Journal Articles

CD4+ T cells play distinct roles during the priming versus effector phases of immune checkpoint therapy-dependent tumor elimination by CD8+ T cells Featured  

(1) Ameh S (2) Theisen DJ (3) Thapa M (4) Turner JS (5) Rangarajan A (6) Nelson CA (7) Schmitz AJ (8) Song Y (9) Medrano RFV (10) Arthur CD (11) White JM (12) Sheehan KCF (13) Fremont DH (14) Ellebedy AH (15) Sultan H (16) Schreiber RD

Cancer immunology research

Ameh et al. studied the role of CD4+ T cells in mouse models during ICB treatment. CD4+ T cells were crucial for priming and effector phases to induce tumor rejection. During the effector phase, CD4+ T cells helped reinvigorate tumor-specific CD8+ T cells. CD40/CD40L signaling was vital for CD4+ T cell function during priming, while IL-2 and IFNγ were necessary for antitumor CD8+ T cell responses during the effector phase.

(1) Ameh S (2) Theisen DJ (3) Thapa M (4) Turner JS (5) Rangarajan A (6) Nelson CA (7) Schmitz AJ (8) Song Y (9) Medrano RFV (10) Arthur CD (11) White JM (12) Sheehan KCF (13) Fremont DH (14) Ellebedy AH (15) Sultan H (16) Schreiber RD

Cancer immunology research

Ameh et al. studied the role of CD4+ T cells in mouse models during ICB treatment. CD4+ T cells were crucial for priming and effector phases to induce tumor rejection. During the effector phase, CD4+ T cells helped reinvigorate tumor-specific CD8+ T cells. CD40/CD40L signaling was vital for CD4+ T cell function during priming, while IL-2 and IFNγ were necessary for antitumor CD8+ T cell responses during the effector phase.

ABSTRACT: It is well established that CD4⁺ T cells play a critical role in facilitating immune checkpoint therapy (ICT). Although CD4+ T-cell function in lymph nodes during CD8⁺ T-cell priming has been well investigated, their requirement at the effector phase in the tumor is only now beginning to be appreciated. Herein, we used our major histocompatibility complex class II-negative (MHC-II-) sarcoma models to confirm that CD4⁺ T cells are essential not only during T-cell priming, but also to maintain T-cell effector function within the tumor. Depleting CD4⁺ T cells at the effector phase, after CD8+ T-cell priming had occurred, abolished ICT-induced tumor rejection despite the detection of tumor-specific CD8⁺ T cells and their intratumoral accumulation. CD4⁺ T cells were required for functional reinvigoration of CD8⁺ tumor-infiltrating lymphocytes (TIL) by ICT, leading to enhanced cytokine production, expression of cytotoxicity, and reduced exhaustion-without affecting CD8+ T-cell proliferation. Mechanistically, CD4⁺ T-cell function at the effector phase did not require CD40/CD40L signaling, which is necessary for efficient priming, but rather depended on IL-2 and IFNγ. Using a TCR-mimic monoclonal antibody (1G10) specific for the dominant neoantigen:I-Aᵇ complex on antigen-presenting cells formed during T3 sarcoma challenge, we further showed that ongoing MHC-II neoantigen presentation was necessary to sustain CD4⁺ T-cell help after priming. These findings reveal temporally distinct requirements for CD4⁺ T-cell help and establish a need for continuous CD4⁺/CD8⁺ T-cell cooperation as a prerequisite for anti-PD-1/anti-CTLA-4 ICT efficacy against MHC-II- tumors.

Author Info: (1) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (2) Washington University in St. Louis St. Louis, MO United States. ROR: https://

Author Info: (1) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (2) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (3) Washington University in St Louis St Louis United States. (4) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (5) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (6) Washington University in St. Louis United States. ROR: https://ror.org/01yc7t268 (7) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (8) Washington University in St. Louis St. Louis, Missouri United States. ROR: https://ror.org/01yc7t268 (9) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (10) Washington University in St. Louis Saint Louis, MO United States. ROR: https://ror.org/01yc7t268 (11) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (12) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268 (13) Washington University in St. Louis St. Louis, Missouri United States. ROR: https://ror.org/01yc7t268 (14) Washington University in St. Louis St. Louis, Missouri United States. ROR: https://ror.org/01yc7t268 (15) Washington University in St. Louis St. Louis, Missouri United States. ROR: https://ror.org/01yc7t268 (16) Washington University in St. Louis St. Louis, MO United States. ROR: https://ror.org/01yc7t268

Citation: Cancer Immunol Res 2026 Jul 16 Epub07/16/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42462143

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Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies Spotlight 

(1) Meyerhoff RR (2) Chen A (3) O'Brien J (4) Anadon CM (5) Lopez Bailon LU (6) Carrion-Estrada D (7) Poysungnoen K (8) Lindenberger J (9) Kemeny G (10) Lyniv L (11) Jain V (12) Chaurio R (13) Plappert N (14) Evangelous T (15) Park CS (16) Sinha A (17) Oduah E (18) Glass C (19) Weinhold K (20) Gregory S (21) Hickey JW (22) Acharya P (23) Ready N (24) Conejo-Garcia JR (25) Williams WB (26) Antonia SJ

Cancer cell

Evaluating patient NSCLC tumors treated with neoadjuvant anti-PD-1 and enriched for tertiary lymphoid structures, Meyerhoff, Chen, and O’brien et al. used transcriptomic data to identify B cell populations, including CD138+ plasma cells, and then performed single-cell sequencing to identify tumor-targeting BCRs and generate recombinant antibodies. The lead antibody, PC-1, recognized citrullinated antigens on tumor and pro-tumor myeloid cells, dependent on their expression of the citrullination enzyme PAD2. Incorporation of PC-1 into a CAR T cell mediated tumor control in mouse models, without evidence of off-tumor toxicity.

Contributed by Lauren Hitchings

(1) Meyerhoff RR (2) Chen A (3) O'Brien J (4) Anadon CM (5) Lopez Bailon LU (6) Carrion-Estrada D (7) Poysungnoen K (8) Lindenberger J (9) Kemeny G (10) Lyniv L (11) Jain V (12) Chaurio R (13) Plappert N (14) Evangelous T (15) Park CS (16) Sinha A (17) Oduah E (18) Glass C (19) Weinhold K (20) Gregory S (21) Hickey JW (22) Acharya P (23) Ready N (24) Conejo-Garcia JR (25) Williams WB (26) Antonia SJ

Cancer cell

Evaluating patient NSCLC tumors treated with neoadjuvant anti-PD-1 and enriched for tertiary lymphoid structures, Meyerhoff, Chen, and O’brien et al. used transcriptomic data to identify B cell populations, including CD138+ plasma cells, and then performed single-cell sequencing to identify tumor-targeting BCRs and generate recombinant antibodies. The lead antibody, PC-1, recognized citrullinated antigens on tumor and pro-tumor myeloid cells, dependent on their expression of the citrullination enzyme PAD2. Incorporation of PC-1 into a CAR T cell mediated tumor control in mouse models, without evidence of off-tumor toxicity.

Contributed by Lauren Hitchings

ABSTRACT: The role of tumor-infiltrating B cells (TIL-Bs) in shaping anti-tumor responses in the context of immune checkpoint blockade remains incompletely understood. Here, we interrogate the humoral response in resected lung tumors from patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant PD-1 blockade. We find that tumors orchestrate tertiary lymphoid structures with CD138(+) plasma cells, from which we clone recombinant monoclonal antibodies (mAbs) using B cell receptors (BCRs) exhibiting somatic hypermutation and class switching. Several mAbs bind cell-surface citrullinated proteins, characteristic of cancer cells. Chimeric antigen receptor (CAR) T redirected with the soluble chain fragment variable (scFv) of our lead candidate antibody (PC-1) specifically target tumor cells and tumor-promoting myeloid cells in vivo without off-target activity. Moreover, ablation of the citrullination enzyme PADI2 in tumor-bearing mice eliminates reactivity to PC-1 and cytotoxic killing by the CAR. Our results implicate a therapeutic potential for tumor-infiltrating plasma cells that may be harnessed for cancer treatment.

Author Info: (1) Division of Interventional Radiology, Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: meyerhr@mskcc.org. (2) Division of

Author Info: (1) Division of Interventional Radiology, Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: meyerhr@mskcc.org. (2) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (3) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (4) Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA. (5) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (6) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (7) Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA. (8) Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA. (9) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (10) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (11) Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27710, USA. (12) Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA. (13) Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA. (14) Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. (15) Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA. (16) Department of Chemistry, Duke University, Durham, NC 27710, USA; Department of Computer Science, Duke University, Durham, NC 27710, USA. (17) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (18) Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA. (19) Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA. (20) Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27710, USA. (21) Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27710, USA. (22) Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. (23) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. (24) Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA. (25) Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: wilton.williams@duke.edu. (26) Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: scott.antonia@duke.edu.

Citation: Cancer Cell 2026 Jul 27 Epub07/27/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42508408

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Tertiary lymphoid structures harbour stem-like tumour-specific T cells Spotlight 

(1) Afeyan AB (2) Nagler A (3) Tu CR (4) Roberti De Oliveira G (5) Simsek B (6) Seager MD (7) El Ahmar N (8) Sax HE (9) Lin E (10) Sud A (11) Borji M (12) Forman C (13) Liu S (14) Ott PA (15) Choueiri TK (16) Abelin JG (17) Burack R (18) Li S (19) Livak KJ (20) Tyekucheva S (21) Keskin DB (22) Chen F (23) Atkins MB (24) Simon JM (25) Signoretti S (26) Oliveira G (27) Braun DA (28) Wu CJ

Nature

Afeyan, Nagler, and Tu et al. investigated how tertiary lymphoid structures (TLSs) impact phenotypic properties of tumor-specific T cells in treatment-naive renal carcinoma (RCC). Compared to TLS- tumors, TLS+ tumors were associated with increased numbers of exhausted CD8+ T cells (Tex) as well as IFN-stimulated CD8+ T cells and proliferating T cells, although CD8+ T cells exhibited greater exhaustion in TLS- tumors. 12% of tumor-specific clonotypes in TLSs exhibited a stem-like progenitor exhausted phenotype (Tpex) associated with favorable antitumor immunity. CD163+ immunosuppressive TAMs mapped to TLS boundaries with Tex cells.

Contributed by Katherine Turner

(1) Afeyan AB (2) Nagler A (3) Tu CR (4) Roberti De Oliveira G (5) Simsek B (6) Seager MD (7) El Ahmar N (8) Sax HE (9) Lin E (10) Sud A (11) Borji M (12) Forman C (13) Liu S (14) Ott PA (15) Choueiri TK (16) Abelin JG (17) Burack R (18) Li S (19) Livak KJ (20) Tyekucheva S (21) Keskin DB (22) Chen F (23) Atkins MB (24) Simon JM (25) Signoretti S (26) Oliveira G (27) Braun DA (28) Wu CJ

Nature

Afeyan, Nagler, and Tu et al. investigated how tertiary lymphoid structures (TLSs) impact phenotypic properties of tumor-specific T cells in treatment-naive renal carcinoma (RCC). Compared to TLS- tumors, TLS+ tumors were associated with increased numbers of exhausted CD8+ T cells (Tex) as well as IFN-stimulated CD8+ T cells and proliferating T cells, although CD8+ T cells exhibited greater exhaustion in TLS- tumors. 12% of tumor-specific clonotypes in TLSs exhibited a stem-like progenitor exhausted phenotype (Tpex) associated with favorable antitumor immunity. CD163+ immunosuppressive TAMs mapped to TLS boundaries with Tex cells.

Contributed by Katherine Turner

ABSTRACT: Tertiary lymphoid structures (TLSs) are associated with improved responses to immune checkpoint blockade across solid tumours(1,2), but how they impact the phenotypic properties of tumour-specific T cells remains unclear. Here we found, across 24 treatment-naive renal cell carcinoma (RCC) tumours, that TLS-containing tumours are more heavily infiltrated by exhausted CD8(+) T cells and have a reduced terminal exhaustion transcriptional program compared with TLS(-) tumours. Specificity screening of 554 T cell clonotypes expanded within the microenvironment of 6 RCC tumours revealed 82 TCRs that were reactive against tumour cells and/or RCC antigens. A subset of tumour-specific T cell clonotypes (12%) was enriched within TLSs, and these expressed an increased program of stem-like progenitor exhaustion, associated with favourable anti-tumour immunity. However, in 60 independent RCC tumours, macrophages within tumour margins of TLS-containing tumours had an inferred immunosuppressive phenotype and were colocalized with exhausted putative tumour-reactive T cells in a subgroup that was further analysed, therefore supporting this mode of immune evasion as a counterbalance to T cell immune pressure. Our data reveal that TLSs are reservoirs of tumour-specific T cells with stem-like progenitor features that could be leveraged by T cell immunotherapies.

Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (2) Department of Medical Oncology, Dana-Farber Cancer I

Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (2) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (3) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. (4) Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. (5) Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. (6) Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. (7) Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. (8) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (9) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (10) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK. (11) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (12) Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. (13) Broad Institute of MIT and Harvard, Cambridge, MA, USA. Ragon Institute of MGB, MIT and Harvard, Cambridge, MA, USA. (14) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (15) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (16) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (17) University of Rochester Medical Center, Department of Pathology and Laboratory Medicine, Rochester, NY, USA. (18) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. (19) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. (20) Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. (21) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Computer Science, Metropolitan College, Boston University, Boston, MA, USA. Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark. (22) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (23) Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA. (24) Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. (25) Harvard Medical School, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. (26) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. giacomo_oliveira@dfci.harvard.edu. Harvard Medical School, Boston, MA, USA. giacomo_oliveira@dfci.harvard.edu. Broad Institute of MIT and Harvard, Cambridge, MA, USA. giacomo_oliveira@dfci.harvard.edu. (27) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. david.braun@yale.edu. Section of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. david.braun@yale.edu. Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. david.braun@yale.edu. (28) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. catherine_wu@dfci.harvard.edu. Harvard Medical School, Boston, MA, USA. catherine_wu@dfci.harvard.edu. Broad Institute of MIT and Harvard, Cambridge, MA, USA. catherine_wu@dfci.harvard.edu.

Citation: Nature 2026 Jul 22 Epub07/22/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42486979

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Subclinical cholestasis is a hallmark of gut dysbiosis causing resistance to cancer immunotherapy

Spotlight 

Anne-Laure Mallard de La Varende (1); Ai-Ling Tian,1 Simon Thomas (1); Imran Lahmar (1); Meriem Messaoudene (2); Sijing Li (3); Omar Motiño (3,4); Hortense Guillaume-dit-Taunière (1); Valerio Iebba (1); Yoan Hurtado (1); Thao-Nguyen Pham (1); Cassandra Thélémaque (1); Miguel Araujo-Voces (1); Deborah Suissa (1); Pierre Ly (1); Ella Reich (1); Giacomo Vitali (5); Bryan Thierry Arlunno (1); Sylvere Durand (6); Fanny Aprahamian (6); Marion Leduc (3,6); Sabrina Forveille (3,6); Oliver Kepp (3,6); Carlos de la Calle-Fabregat (7); Angela Schippers (8); Norbert Wagner (8); Pierre-Edouard Fournier (9); Kenya Honda (10,11,12); Federica Marmorino (13); Chiara Cremolini (13,14); Saman Maleki Vareki (15,16,17,18).

Cancer Cell

Mallard de La Varende et al. showed that gut dysbiosis following treatment with antibiotics or antibiotic-associated species led to loss of secondary bile acids (BAs), increased tauro-conjugated primary BAs, downregulation of MAdCAM-1 in the ilium, and increased γ-glutamyl transferase (γ-GT) in serum, supporting TIME reprogramming, T cell exhaustion, and resistance to anti-PD-1 in tumor-bearing mice. Resistance could be overcome by performing FMT, supplementing secondary BAs, or using an ilium-specific FXR agonist. In patients, resistance was associated with subclinical cholestasis (elevated γ-GT), which predicted poor response.

Contributed by Lauren Hitchings

Anne-Laure Mallard de La Varende (1); Ai-Ling Tian,1 Simon Thomas (1); Imran Lahmar (1); Meriem Messaoudene (2); Sijing Li (3); Omar Motiño (3,4); Hortense Guillaume-dit-Taunière (1); Valerio Iebba (1); Yoan Hurtado (1); Thao-Nguyen Pham (1); Cassandra Thélémaque (1); Miguel Araujo-Voces (1); Deborah Suissa (1); Pierre Ly (1); Ella Reich (1); Giacomo Vitali (5); Bryan Thierry Arlunno (1); Sylvere Durand (6); Fanny Aprahamian (6); Marion Leduc (3,6); Sabrina Forveille (3,6); Oliver Kepp (3,6); Carlos de la Calle-Fabregat (7); Angela Schippers (8); Norbert Wagner (8); Pierre-Edouard Fournier (9); Kenya Honda (10,11,12); Federica Marmorino (13); Chiara Cremolini (13,14); Saman Maleki Vareki (15,16,17,18).

Cancer Cell

Mallard de La Varende et al. showed that gut dysbiosis following treatment with antibiotics or antibiotic-associated species led to loss of secondary bile acids (BAs), increased tauro-conjugated primary BAs, downregulation of MAdCAM-1 in the ilium, and increased γ-glutamyl transferase (γ-GT) in serum, supporting TIME reprogramming, T cell exhaustion, and resistance to anti-PD-1 in tumor-bearing mice. Resistance could be overcome by performing FMT, supplementing secondary BAs, or using an ilium-specific FXR agonist. In patients, resistance was associated with subclinical cholestasis (elevated γ-GT), which predicted poor response.

Contributed by Lauren Hitchings

ABSTRACT: Gut dysbiosis compromises cancer immunosurveillance by downregulating ileal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but the metabolic landscape associated with gut dysbiosis remains elusive. Here, we show that antibiotics (ABX) or ABX-associated Enterocloster species lead to the loss of secondary bile acids (BAs) including deoxycholic acid (DCA) and the accumulation of tauro-conjugated primary BAs (tauro-chenodeoxycholic acid [TCDCA] and tauro-β-muricholic acid [T-βMCA]) from the alternative pathway in the plasma of patients and mice. Fecal microbial transplantation (FMT), the ileum-specific farnesoid X receptor (FXR) agonist fexaramine, or glycodeoxycholic acid (GDCA) compen- sated dysbiosis-associated BA abnormalities and circumvent primary resistance to PD-1 blockade. GDCA curtailed ABX-induced MAdCAM-1 downregulation and T cell exhaustion in tumors. Subclinical cholestasis defined by elevation of γ-glutamyl transferase (γGT) correlated with increased TCDCA and decreased sMAdCAM-1 in plasma and predicted poor survival in multivariate analyses in six cohorts of patients who received immunotherapy. Hence, subclinical cholestasis accompanies gut dysbiosis, paving the way to immunoresistance.

Author Info: 1- Université Paris-Saclay, Gustave Roussy (GRCC), ClinicObiome, Inserm UMR1367, Microbiota and Mucosal Immunity for Cancer Immunotherapy, 94805 Villejuif, France. 2- Centre de rec

Author Info: 1- Université Paris-Saclay, Gustave Roussy (GRCC), ClinicObiome, Inserm UMR1367, Microbiota and Mucosal Immunity for Cancer Immunotherapy, 94805 Villejuif, France. 2- Centre de recherche Du CHUM (CRCHUM), Montréal, QC H2W1T8, Canada. 3- Centre de Recherche des Cordeliers, INSERM U1138, Equipe Labellisée – Ligue Nationale Contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France. 4- Unidad de Excelencia, Instituto de Biomedicina y Genética Molecular de Valladolid, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, 47001 Valladolid, Spain. 5- MetaGenoPolis, INRAe, Université Paris-Saclay 78350 Jouy en Josas, France. 6- Université Paris-Saclay, INSERM US23, Analyse moléculaire, modélisation et imagerie de la maladie Cancéreuse, Plateformes de Métabolomique et de Criblage Cellulaire Haut Débit, 94805 Villejuif, France. 7- Université Paris-Saclay, Gustave Roussy, U1356 Next Generation Immuno-Oncology Research, 94805 Villejuif, France

Citation: Cancer Cell July 2026

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    A Patient-Derived Screen Identifies HDAC Inhibitors as Enhancers of Phagocytosis and Potent Immunotherapy Partners Spotlight 

    (1) Khalaj M (2) Burden AT (3) Gutierrez ML (4) Hoonsbeen SC (5) Nejad P (6) Raveh T (7) Young JS (8) Fattahi F (9) Weissman IL

    Cancer immunology research

    Khalaj et al. performed a small molecule screen of FDA-approved compounds on CD11b+ tumor-associated microglia/macrophages isolated from patient GBM, and identified histone deacetylase (HDAC) inhibitors as enhancers of TAM phagocytosis. HDAC inhibitors increased phagocytosis across multiple TAM-GBM pairs, and showed synergy with CD47 blockade ex vivo. In an orthotopic patient-derived GBM xenograft model, Pracinostat combined with anti-CD47 slowed tumor growth and extended survival. Pracinostat reprogrammed TAMs toward an NF-κB-driven inflammatory state, and epigenetically primed FcγR-mediated phagocytic machinery.

    Contributed by Shishir Pant

    (1) Khalaj M (2) Burden AT (3) Gutierrez ML (4) Hoonsbeen SC (5) Nejad P (6) Raveh T (7) Young JS (8) Fattahi F (9) Weissman IL

    Cancer immunology research

    Khalaj et al. performed a small molecule screen of FDA-approved compounds on CD11b+ tumor-associated microglia/macrophages isolated from patient GBM, and identified histone deacetylase (HDAC) inhibitors as enhancers of TAM phagocytosis. HDAC inhibitors increased phagocytosis across multiple TAM-GBM pairs, and showed synergy with CD47 blockade ex vivo. In an orthotopic patient-derived GBM xenograft model, Pracinostat combined with anti-CD47 slowed tumor growth and extended survival. Pracinostat reprogrammed TAMs toward an NF-κB-driven inflammatory state, and epigenetically primed FcγR-mediated phagocytic machinery.

    Contributed by Shishir Pant

    ABSTRACT: Glioblastoma multiforme (GBM) is a lethal brain tumor with limited treatment options. Tumor-associated macrophages and microglia (TAMs) drive immune suppression and tumor progression, making them a key therapeutic target for GBM. Enhancing TAM phagocytosis in GBM has shown promise, particularly with innate checkpoint inhibitors, such as CD47-blocking antibodies. However, small molecule approaches, which offer tunable and potentially synergistic mechanisms, remain underexplored in this context. In this study, we conducted a large-scale small molecule screen on primary TAMs isolated directly from GBM patient tumors, testing 1,365 compounds to identify drugs that enhance TAM phagocytosis. This screen revealed enrichment for histone deacetylase (HDAC)-targeting drugs among the top hits. HDAC inhibitors enhanced phagocytosis of cancer cells across multiple primary human TAM-GBM combinations, and synergized with CD47 blockade ex vivo. In a xenograft GBM model, Pracinostat suppressed tumor growth and extended survival, with additive benefit when combined with CD47 antibodies. RNA-sequencing and H3K27Ac CUT&Tag profiling of Pracinostat-treated TAMs in vivo revealed a two-tier mechanism: transcriptional reprogramming toward a pro-inflammatory state via NF-κB activation, and epigenetic priming of FcγR-mediated phagocytic machinery, providing a mechanistic basis for the observed synergy with CD47 blockade. Our findings establish a patient-first functional screening platform for identifying TAM-reprogramming therapeutics in GBM, validate HDAC inhibitors as a lead class that potentiates innate checkpoint immunotherapy, and provide additional candidate compounds for clinical investigation.

    Author Info: (1) Stanford Medicine Stanford United States. ROR: https://ror.org/03mtd9a03 (2) Stanford Medicine United States. ROR: https://ror.org/03mtd9a03 (3) University of California, San F

    Author Info: (1) Stanford Medicine Stanford United States. ROR: https://ror.org/03mtd9a03 (2) Stanford Medicine United States. ROR: https://ror.org/03mtd9a03 (3) University of California, San Francisco San Francisco United States. ROR: https://ror.org/043mz5j54 (4) University of California San Francisco Medical Center San Francisco United States. ROR: https://ror.org/01t8svj65 (5) Stanford Medicine Stanford United States. ROR: https://ror.org/03mtd9a03 (6) Stanford University California 94305-5439, CA United States. ROR: https://ror.org/00f54p054 (7) University of California, San Francisco San Francisco, CA United States. ROR: https://ror.org/043mz5j54 (8) University of California, San Francisco San Francisco, CA United States. ROR: https://ror.org/043mz5j54 (9) Stanford University Stanford University, CA United States. ROR: https://ror.org/00f54p054

    Citation: Cancer Immunol Res 2026 Jul 14 Epub07/14/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42446904

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    Tim-3 Sustains Tumor Treg Stability and Function, Limiting Checkpoint Blockade Therapy Efficacy Spotlight 

    (1) Banerjee H (2) Onyekachi OV (3) Nieves-Rosado H (4) Murter BM (5) Kulkarni A (6) Pandey SP (7) Cardona E (8) Dougherty JE (9) Li H (10) Upadhyay P (11) Hinterleitner R (12) Ferris RL (13) Kane LP

    Cancer immunology research

    Banerjee et al. showed that Tim3 expression on tumor-infiltrating Tregs was required for their survival and suppressive function via Akt-FOXO1 signaling. Treg-specific Tim3 deletion in an MC38 model reduced tumor-infiltrating Tregs and CD25 expression, impaired Treg survival, delayed CD8+ T cell exhaustion, enhanced CD8+ proliferation, and reduced tumor burden, without disrupting peripheral homeostasis. Delayed Tim3 deletion in Tregs was sufficient to slow tumor growth and augment CD8+ responses, and Treg-specific Tim3 loss synergized with ICB in a resistant B16F10 model. In HNSCC, low Tim3 expression correlated with response to anti-PD-1/Lag3 ICB.

    Contributed by Shishir Pant

    (1) Banerjee H (2) Onyekachi OV (3) Nieves-Rosado H (4) Murter BM (5) Kulkarni A (6) Pandey SP (7) Cardona E (8) Dougherty JE (9) Li H (10) Upadhyay P (11) Hinterleitner R (12) Ferris RL (13) Kane LP

    Cancer immunology research

    Banerjee et al. showed that Tim3 expression on tumor-infiltrating Tregs was required for their survival and suppressive function via Akt-FOXO1 signaling. Treg-specific Tim3 deletion in an MC38 model reduced tumor-infiltrating Tregs and CD25 expression, impaired Treg survival, delayed CD8+ T cell exhaustion, enhanced CD8+ proliferation, and reduced tumor burden, without disrupting peripheral homeostasis. Delayed Tim3 deletion in Tregs was sufficient to slow tumor growth and augment CD8+ responses, and Treg-specific Tim3 loss synergized with ICB in a resistant B16F10 model. In HNSCC, low Tim3 expression correlated with response to anti-PD-1/Lag3 ICB.

    Contributed by Shishir Pant

    ABSTRACT: Regulatory T cells (Treg) act as a powerful barrier to effective antitumor immunity. Although manipulating Treg is a promising anticancer strategy, doing so while sparing general immune tolerance has been a challenge. Identifying factors specifically expressed in tumor-infiltrating Treg is therefore important for better understanding cancer pathogenesis and identifying novel therapeutic targets that enhance antitumor immunity. We show that T cell Immunoglobulin and Mucin 3 (Tim-3) expression on tumor Treg is required for the function and survival of these cells, in part through Akt and FOXO1 signaling. Deleting Tim-3 in Treg leads to delayed tumor-specific T-cell exhaustion and lower tumor burden, without altering peripheral homeostasis. Similar effects were noted when Tim-3 was only deleted from half of the Treg or when deletion was delayed until after tumor inoculation. Moreover, Treg-specific deletion of Tim-3 cooperated with PD-1 checkpoint blockade to sensitize an immunotherapy-resistant tumor model. In addition, a decrease in Tim-3+ tumor Treg correlated with responsiveness to PD-1/LAG-3 combination checkpoint blockade in a human clinical trial. Overall, our data provide evidence that Tim3-expressing Treg are a promising target to modulate tumor-specific immune responses.

    Author Info: (1) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (2) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305

    Author Info: (1) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (2) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (3) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (4) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (5) University of North Carolina at Chapel Hill Chapel Hill, NC United States. ROR: https://ror.org/0130frc33 (6) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (7) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (8) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (9) University of Pittsburgh Pittsburgh, PA United States. (10) University of North Carolina at Chapel Hill Chapel Hill, NC United States. ROR: https://ror.org/0130frc33 (11) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305 (12) University of North Carolina Hospitals Chapel Hill, NC United States. ROR: https://ror.org/0355zfr67 (13) University of Pittsburgh Pittsburgh, PA United States. ROR: https://ror.org/01an3r305

    Citation: Cancer Immunol Res 2026 Jul 15 Epub07/15/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42455126

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    A distinct antigen presentation pathway drives potent T cell immunity in lipid nanoparticle-based mRNA vaccines Spotlight 

    (1) Muro R (2) Wang S (3) Ito-Kureha T (4) Huynh HH (5) Kobiyama K (6) Sugita T (7) Okamoto K (8) Nakano K (9) Okamura T (10) Kubo M (11) Ishii KJ (12) Nitta T (13) Takayanagi H

    Science advances | Free PMC Article

    Muro and Wang et al. studied mechanisms by which lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccines induce significantly higher levels of antigen-specific cytotoxic T cells and T cell-dependent antibodies compared to conventional adjuvant-based immunization. Using model antigens, mRNA-LNP induced Th1-skewed murine CD4+ T cell differentiation, followed by production of class-switched IgGs (IgG2b and IgG2c) and long-term cytotoxic CD8+ T cells. Unlike traditional cDC1-mediated cross-presentation, mRNA-LNPs were primarily found in migratory cDC2 cells in draining lymph nodes, resulting in strong, persistent antigen presentation.

    Contributed by Katherine Turner

    (1) Muro R (2) Wang S (3) Ito-Kureha T (4) Huynh HH (5) Kobiyama K (6) Sugita T (7) Okamoto K (8) Nakano K (9) Okamura T (10) Kubo M (11) Ishii KJ (12) Nitta T (13) Takayanagi H

    Science advances | Free PMC Article

    Muro and Wang et al. studied mechanisms by which lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccines induce significantly higher levels of antigen-specific cytotoxic T cells and T cell-dependent antibodies compared to conventional adjuvant-based immunization. Using model antigens, mRNA-LNP induced Th1-skewed murine CD4+ T cell differentiation, followed by production of class-switched IgGs (IgG2b and IgG2c) and long-term cytotoxic CD8+ T cells. Unlike traditional cDC1-mediated cross-presentation, mRNA-LNPs were primarily found in migratory cDC2 cells in draining lymph nodes, resulting in strong, persistent antigen presentation.

    Contributed by Katherine Turner

    ABSTRACT: Lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccines trigger the potent differentiation of antigen-specific cytotoxic CD8 T cells in addition to antibody production. Despite its high immunogenicity, the cellular mechanisms by which mRNA-LNP induces such unusual immune responses remain largely unclear. Here, we show that mRNA-LNP induces potent and long-lasting CD8 T cell expansion through an antigen presentation mechanism that differs from that of conventional adjuvants. In mice immunized with mRNA-LNP, the number of antigen-specific CD8 T cells was one order of magnitude higher than that induced by combining antigen proteins with immunostimulants such as lipopolysaccharide or polyinosinic:polycytidinic acid. Intramuscularly administered mRNA-LNPs were mainly taken up by migratory type 2 conventional dendritic cells in draining lymph nodes, resulting in notably strong and persistent antigen presentation through major histocompatibility complex class I. Furthermore, CD8 T cell induction by mRNA-LNP required migratory dendritic cells but not the traditional cross-presentation pathway that is otherwise essential for antiviral and antitumor immunity. Thus, the mRNA-LNP formulation exerts unconventional immune responses through a different antigen-presentation pathway from conventional component vaccines.

    Author Info: (1) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Division of Molecular Pathology, Research Institute for Bi

    Author Info: (1) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Division of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. (2) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. (3) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. (4) Division of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. (5) Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Division of Rheumatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States. (6) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. (7) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Division of Immune Environment Dynamics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. Immune Network Research Unit, Institute for Frontier Science Initiative InFiniti, Kanazawa University, Kanazawa, Japan. (8) Department of Laboratory Animal Medicine, National Institute of Global Health and Medicine, Japan Institute for Health and Security (JIHS), Tokyo, Japan. (9) Department of Laboratory Animal Medicine, National Institute of Global Health and Medicine, Japan Institute for Health and Security (JIHS), Tokyo, Japan. (10) Kyoto University Immunomonitoring Center, Liaison Office, Kyoto University, Kyoto, Japan. Department of Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. (11) Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. (12) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Division of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. (13) Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

    Citation: Sci Adv 2026 Jul 17 12:eaec7827 Epub07/17/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42467780

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    IL7-Receptor-Targeted CAR T-Cell Therapy for T-Cell Acute Lymphoblastic Leukemia Spotlight 

    (1) Hocine HR (2) Ganbaatar U (3) Amador-Molina A (4) Banerjee S (5) Misawa K (6) Rubino V (7) Ankola P (8) Fong C (9) Xiong Y (10) Vista WR (11) Bellis RY (12) Chintala NK (13) Curran KJ (14) Sulis ML (15) Park JH (16) Kung AL (17) Adusumilli PS

    Nature communications

    Hocine, Ganbaatar, and Amador-Molina et al. developed an IL7Rα (CD127)-targeted chimeric antigen receptor (CAR) T cells and demonstrated their efficacy against T-ALL in vitro and in vivo, including in a patient-derived xenograft model using matched patient-derived CAR T cells. Low-affinity CAR T cells outperformed high-affinity cells, but maintained higher expression of CD127, putting them at risk of fratricide after tumor eradication. To reduce fratricide, genetic KO of CD127, a natural selection method, and co-culture with dasatinib (a tyrosine kinase inhibitor), during manufacturing were each tested, with dasatinib emerging as the most viable option.

    Contributed by Lauren Hitchings

    (1) Hocine HR (2) Ganbaatar U (3) Amador-Molina A (4) Banerjee S (5) Misawa K (6) Rubino V (7) Ankola P (8) Fong C (9) Xiong Y (10) Vista WR (11) Bellis RY (12) Chintala NK (13) Curran KJ (14) Sulis ML (15) Park JH (16) Kung AL (17) Adusumilli PS

    Nature communications

    Hocine, Ganbaatar, and Amador-Molina et al. developed an IL7Rα (CD127)-targeted chimeric antigen receptor (CAR) T cells and demonstrated their efficacy against T-ALL in vitro and in vivo, including in a patient-derived xenograft model using matched patient-derived CAR T cells. Low-affinity CAR T cells outperformed high-affinity cells, but maintained higher expression of CD127, putting them at risk of fratricide after tumor eradication. To reduce fratricide, genetic KO of CD127, a natural selection method, and co-culture with dasatinib (a tyrosine kinase inhibitor), during manufacturing were each tested, with dasatinib emerging as the most viable option.

    Contributed by Lauren Hitchings

    ABSTRACT: On the basis that T-cell acute lymphoblastic leukemia (T-ALL) cells overexpress IL7 receptor (IL7R), which promotes resistance to chemotherapy and disease relapse, here we develop IL7Rα (CD127)-targeted chimeric antigen receptor (CAR) T cells with low- and high-affinity single-chain variable fragments. We establish the antitumor efficacy of CD127 CAR against T-ALL cells in vitro, in female mouse models of T-ALL, and against blasts from patients with T-ALL using the patients' own T cells transduced with CD127 CAR. Antitumor efficacy is higher with low-affinity CAR T cells than high-affinity CAR T cells, albeit with fratricide of CAR T cells following eradication of CD127-overexpressing blasts. CRISPR-Cas9 knockout of CD127 eliminates fratricide at the risk of prolonged lymphopenia in vivo. To overcome fratricide, we investigate short-term ( < 7 days) co-culture with or without dasatinib, a tyrosine kinase inhibitor, versus a natural selection method (10 days) and demonstrate that co-culturing with dasatinib facilitates higher CAR T-cell yield, improved fitness, and preserved functionality. In vivo, dasatinib can be used to temporarily and reversibly suppress CAR T-cell activity. With this supporting translational data, we are initiating a trial with low-affinity CD127 CAR T cells for adult and pediatric patients with relapsed or refractory T-ALL.

    Author Info: (1) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (2) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer

    Author Info: (1) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (2) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (3) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (4) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (5) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (6) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (7) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (8) Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. (9) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (10) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (11) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (12) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (13) Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. (14) Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. (15) Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. (16) Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. (17) Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. adusumip@mskcc.org. Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. adusumip@mskcc.org.

    Citation: Nat Commun 2026 Jul 15 Epub07/15/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42457686

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    Dendritic cells control tertiary lymphoid structure development and maintenance in cancer Featured  

    (1) Mattiuz R (2) Boumelha J (3) Aerakis E (4) Le Berichel J (5) Hamon P (6) Halasz L (7) Vaidya A (8) Soong BY (9) Radkevich E (10) Kim HM (11) Park MD (12) Donne R (13) Troncoso L (14) Kaplan RA (15) Hennequin C (16) Hern‡ndez-Verdin I (17) L—pez L (18) Rentzeperis F (19) D'Souza D (20) Kaiza ME (21) MacFawn IP (22) Belabed M (23) Mestrallet G (24) Humblin E (25) Merand R (26) Hegde S (27) Lone JC (28) Ioannou G (29) Ozbey S (30) Figueiredo I (31) Tepper A (32) Merarda H (33) Serhan N (34) Schaefer MM (35) An J (36) Ohara RA (37) Nemeth E (38) Goldstein S (39) Reid AM (40) Noureddine M (41) Tabachnikova A (42) Piperno GM (43) Tsoumakidou M (44) Ahmed J (45) Polydorides AD (46) Bhardwaj N (47) Lujambio A (48) Chen Z (49) Gonzalez Kozlova E (50) Kim-Schulze S (51) Brody JD (52) Schotsaert M (53) Moussion C (54) Gnjatic S (55) Roudko V (56) Ginhoux F (57) Murphy KM (58) Sauts-Fridman C (59) Fridman WH (60) Brown BD (61) Marron TU (62) Benvenuti F (63) Cyster JG (64) Salmon H (65) Bruno TC (66) Joshi NS (67) Kamphorst AO (68) Merad M

    Science

    Mattiuz et al. assessed the role of dendritic cells in TLS formation and maintenance. Mature cDC1s were found to play essential roles, with TLS formation being dependent on maturation of cDC1s and their cross-presentation to T cells in the TDLN, followed by T cell recruitment to the tumor. Over time, maintenance of TLSs required the presence of cDC1s and cDC1 migration to CCR7 ligand-enriched stromal hubs, MHC-I and MHC-II antigen presentation to T cells, and CD40 signaling.

    (1) Mattiuz R (2) Boumelha J (3) Aerakis E (4) Le Berichel J (5) Hamon P (6) Halasz L (7) Vaidya A (8) Soong BY (9) Radkevich E (10) Kim HM (11) Park MD (12) Donne R (13) Troncoso L (14) Kaplan RA (15) Hennequin C (16) Hern‡ndez-Verdin I (17) L—pez L (18) Rentzeperis F (19) D'Souza D (20) Kaiza ME (21) MacFawn IP (22) Belabed M (23) Mestrallet G (24) Humblin E (25) Merand R (26) Hegde S (27) Lone JC (28) Ioannou G (29) Ozbey S (30) Figueiredo I (31) Tepper A (32) Merarda H (33) Serhan N (34) Schaefer MM (35) An J (36) Ohara RA (37) Nemeth E (38) Goldstein S (39) Reid AM (40) Noureddine M (41) Tabachnikova A (42) Piperno GM (43) Tsoumakidou M (44) Ahmed J (45) Polydorides AD (46) Bhardwaj N (47) Lujambio A (48) Chen Z (49) Gonzalez Kozlova E (50) Kim-Schulze S (51) Brody JD (52) Schotsaert M (53) Moussion C (54) Gnjatic S (55) Roudko V (56) Ginhoux F (57) Murphy KM (58) Sauts-Fridman C (59) Fridman WH (60) Brown BD (61) Marron TU (62) Benvenuti F (63) Cyster JG (64) Salmon H (65) Bruno TC (66) Joshi NS (67) Kamphorst AO (68) Merad M

    Science

    Mattiuz et al. assessed the role of dendritic cells in TLS formation and maintenance. Mature cDC1s were found to play essential roles, with TLS formation being dependent on maturation of cDC1s and their cross-presentation to T cells in the TDLN, followed by T cell recruitment to the tumor. Over time, maintenance of TLSs required the presence of cDC1s and cDC1 migration to CCR7 ligand-enriched stromal hubs, MHC-I and MHC-II antigen presentation to T cells, and CD40 signaling.

    ABSTRACT: Tertiary lymphoid structures (TLSs) are associated with immunotherapy response, yet the mechanisms controlling their formation and maintenance remain unclear. Using spatial transcriptomics and multiplex imaging across human tumors, we found that CCR7+ mature dendritic cells (DCs) accumulate in TLSs. In a mouse non-small cell lung cancer model that forms mature TLSs, we show that early TLS development requires interferon-γ (IFN-γ)-driven type 1 conventional dendritic cell (cDC1) maturation, migration to tumor-draining lymph nodes (tdLNs), and T cell recruitment. As tumors progress, TLSs persist independently of tdLN T cell egress, coinciding with cDC1 accumulation within intratumoral CCL19 stromal hubs. There, cDC1-major histocompatibility complex class 1 (MHC-I) and -MHC-II concomitant antigen presentation, along with CD40 signaling, sustain TLS, T follicular helper (TFH) cell pool, germinal centers, and tumor-specific immunoglobulin G (IgG). These findings highlight local mature cDC1s as key TLS orchestrators and potential targets to enhance antitumor TLS function.

    Author Info: (1) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn Schoo

    Author Info: (1) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (2) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (3) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Institute for Bioinnovation, "Alexander Fleming" Biomedical Sciences Research Center, Vari, Greece. (4) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (5) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (6) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (7) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (8) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (9) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (10) Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. (11) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (12) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (13) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (14) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (15) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (16) Department of Immunology, Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, Sorbonne UniversitŽ, INSERM, UniversitŽ Paris CitŽ, Paris, France. (17) Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy. (18) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (19) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (20) Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. (21) Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. Department of Biology, Grove City College, Grove City, PA, USA. (22) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (23) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (24) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (25) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (26) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (27) GIMM, Gulbenkian Institute for Molecular Medicine and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. (28) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (29) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (30) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (31) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (32) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (33) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (34) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (35) Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. (36) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. (37) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (38) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (39) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (40) Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute and Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (41) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (42) Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy. (43) Institute for Bioinnovation, "Alexander Fleming" Biomedical Sciences Research Center, Vari, Greece. (44) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (45) Henry D. Janowitz Division of Gastroenterology, Department of Medicine, and Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (46) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (47) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (48) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (49) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (50) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (51) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (52) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. GIMM, Gulbenkian Institute for Molecular Medicine and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. Global Health and Emerging Pathogens Institute and Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (53) Genentech, South San Francisco, CA, USA. (54) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (55) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (56) Paris-Saclay University, Gustave Roussy, INSERM U1015, Villejuif, France. (57) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. (58) Department of Immunology, Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, Sorbonne UniversitŽ, INSERM, UniversitŽ Paris CitŽ, Paris, France. (59) Department of Immunology, Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, Sorbonne UniversitŽ, INSERM, UniversitŽ Paris CitŽ, Paris, France. (60) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (61) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Institute for Thoracic Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (62) Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy. (63) Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. (64) Institut Curie, Paris, France. 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Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

    Citation: Science 2026 Jul 16 393:eady1678 Epub07/16/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42462020

    Tags:

    The efficacy of immunotherapy in glioma requires distal B cell responses in tumor-draining lymph nodes Spotlight 

    (1) Kim Y (2) Kang I (3) Kang BH (4) Park WH (5) Kim CW (6) Kim HJ (7) La J (8) Kwon MS (9) Park SH (10) Im SH (11) Kim HC (12) Ku KB (13) Kim M (14) Oh JE (15) Lee HK

    Science immunology

    Kim et al. showed that anti-CTLA-4 efficacy in orthotopic murine glioblastoma (GBM) models was abolished by B cell deficiency and tdLN removal. In WT mice, anti-CTLA-4 increased B cell numbers and GC reactions in tdLNs, but not in the TIME, and therapeutic efficacy required CD4+ T cell help to B cells. While maintaining tumor-reactive CD4+ T cell function in the TIME, in tdLNs, anti-CTLA-4 therapy boosted TFH cell differentiation to support GC B cell clonal expansion and generation of antibody-secreting cells producing tumor-binding class-switched IgG1 antibodies that promoted macrophage-mediated phagocytosis of glioma cells via Fc receptor signaling.

    Contributed by Paula Hochman

    (1) Kim Y (2) Kang I (3) Kang BH (4) Park WH (5) Kim CW (6) Kim HJ (7) La J (8) Kwon MS (9) Park SH (10) Im SH (11) Kim HC (12) Ku KB (13) Kim M (14) Oh JE (15) Lee HK

    Science immunology

    Kim et al. showed that anti-CTLA-4 efficacy in orthotopic murine glioblastoma (GBM) models was abolished by B cell deficiency and tdLN removal. In WT mice, anti-CTLA-4 increased B cell numbers and GC reactions in tdLNs, but not in the TIME, and therapeutic efficacy required CD4+ T cell help to B cells. While maintaining tumor-reactive CD4+ T cell function in the TIME, in tdLNs, anti-CTLA-4 therapy boosted TFH cell differentiation to support GC B cell clonal expansion and generation of antibody-secreting cells producing tumor-binding class-switched IgG1 antibodies that promoted macrophage-mediated phagocytosis of glioma cells via Fc receptor signaling.

    Contributed by Paula Hochman

    ABSTRACT: Humoral immunity, mediated by B cells that mature in germinal centers in lymph nodes (LNs), is essential for adaptive immune responses, but its role in antitumor immunity and responses to immunotherapy remain unclear. Here, we show that activation of B cells in tumor-draining deep cervical LNs (dcLNs) is necessary for the efficacy of CTLA-4 (cytotoxic T lymphocyte-associated protein 4) immune checkpoint blockade in glioma in vivo. Anti-CTLA-4 therapy enhanced T follicular helper cell (T(FH) cell) expansion in dcLNs, leading to germinal center B cell responses, immunoglobulin G (IgG) class switching, and the generation of glioma-reactive antibodies. Glioma-bearing mice lacking antibody-secreting cells did not benefit from CTLA-4 blockade. Distally secreted IgG accumulated in the tumor microenvironment and promoted glioma cell phagocytosis in vivo. These findings define a B cell-dependent mechanism underlying CTLA-4-mediated control of glioma and provide a conceptual framework for future therapeutic strategies in tumor.

    Author Info: (1) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (2) Laboratory of Host D

    Author Info: (1) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (2) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (3) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (4) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (5) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (6) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (7) Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (8) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (9) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (10) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (11) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (12) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Department of Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea. (13) Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (14) Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (15) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Regenerative Medical Research Institute (reMRI) for Aging-Related Diseases, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

    Citation: Sci Immunol 2026 Jul 10 11:eadz2494 Epub07/10/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42430444

    Tags:
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