Journal Articles

NR2F6 deletion revives CAR-T cell function and induces antigen-agnostic immune memory in solid tumors Spotlight 

(1) Humer D (2) Klepsch V (3) Rieder D (4) Hölzl I (5) Schreiber D (6) Lang V (7) Koutník J (8) Peer S (9) Sajinovic T (10) Wille V (11) Fürst A (12) Savic D (13) Diem G (14) Posch W (15) Skvortsova II (16) Krogsdam A (17) Sopper S (18) Kobold S (19) Trajanoski Z (20) Siegmund K (21) Thuille N (22) Gruber T (23) Wolf D (24) Baier G

Nature communications

Dominik and Victoria et al. identified NR2F6 as a T cell-intrinsic metabolic checkpoint for CAR T cells in solid tumors. CRISPR/Cas9-mediated deletion of NR2F6 sustained a TCF1+ progenitor exhausted state and maintained metabolic fitness during chronic antigen stimulation. NR2F6 deletion in CAR T cells increased cytotoxicity, cytokine production, resistance to functional exhaustion, and tumor control in immunocompetent Panc02-EpCAM tumor models. DC-mediated cross-priming with epitope spreading and activation of endogenous immunity generated durable protection against CAR antigen-positive and -negative tumor rechallenge.

Contributed by Shishir Pant

(1) Humer D (2) Klepsch V (3) Rieder D (4) Hölzl I (5) Schreiber D (6) Lang V (7) Koutník J (8) Peer S (9) Sajinovic T (10) Wille V (11) Fürst A (12) Savic D (13) Diem G (14) Posch W (15) Skvortsova II (16) Krogsdam A (17) Sopper S (18) Kobold S (19) Trajanoski Z (20) Siegmund K (21) Thuille N (22) Gruber T (23) Wolf D (24) Baier G

Nature communications

Dominik and Victoria et al. identified NR2F6 as a T cell-intrinsic metabolic checkpoint for CAR T cells in solid tumors. CRISPR/Cas9-mediated deletion of NR2F6 sustained a TCF1+ progenitor exhausted state and maintained metabolic fitness during chronic antigen stimulation. NR2F6 deletion in CAR T cells increased cytotoxicity, cytokine production, resistance to functional exhaustion, and tumor control in immunocompetent Panc02-EpCAM tumor models. DC-mediated cross-priming with epitope spreading and activation of endogenous immunity generated durable protection against CAR antigen-positive and -negative tumor rechallenge.

Contributed by Shishir Pant

ABSTRACT: CAR-T cell therapy is effective in hematologic malignancies but remains challenging in solid tumors owing to antigen heterogeneity and tumor microenvironment-induced exhaustion. Here, gene editing of the nuclear receptor NR2F6 restores CAR-T cell functionality, sustaining a TCF1⁺ progenitor-exhausted phenotype, enhancing metabolic fitness, and preserving cytotoxic potency under chronic antigen exposure. In immunocompetent models, Nr2f6-deficient CAR-T cells suppress solid tumor growth and induce robust, polyclonal host antitumor responses that persist after CAR-T clearance, as demonstrated by tumor re-challenge protection. Although infused CAR-T cells disappear within 2 weeks, durable tumor control coincides with epitope spreading and secondary immune responses, likely via dendritic cell reactivation. Protection against antigen-negative tumors and transferable immunity reveal a dual mode of direct cytotoxicity followed by durable immune reprogramming. This broadened host immunity may offset immune escape driven by antigen heterogeneity or loss, establishing NR2F6 inhibition as a promising CAR-T engineering strategy for durable, antigen-agnostic solid-tumor immunotherapy.

Author Info: (1) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (2) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. victoria

Author Info: (1) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (2) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. victoria.klepsch@i-med.ac.at. (3) Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria. (4) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (5) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (6) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (7) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (8) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck and Tyrolean Cancer Research Institute, Medical University of Innsbruck, Innsbruck, Austria. (9) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (10) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (11) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. Institute of Molecular Immunology, School of Medicine and Health, Technical University of Munich, Munich, Germany. (12) Tyrolean Cancer Research Institute, Innsbruck, Austria. Department of Therapeutic Radiology and Oncology, Medical University Innsbruck, Innsbruck, Austria. (13) Institute of Hygiene and Medical Microbiology Medical University of Innsbruck, Innsbruck, Austria. (14) Institute of Hygiene and Medical Microbiology Medical University of Innsbruck, Innsbruck, Austria. (15) Tyrolean Cancer Research Institute, Innsbruck, Austria. Department of Therapeutic Radiology and Oncology, Medical University Innsbruck, Innsbruck, Austria. (16) Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria. (17) Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck and Tyrolean Cancer Research Institute, Medical University of Innsbruck, Innsbruck, Austria. (18) Institute for Clinical Pharmacology, Klinikum der UniversitŠt MŸnchen, Munich, Germany. German Cancer Consortium, a partnership between LMU Hospital and the DKFZ, Munich, Germany. (19) Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria. (20) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (21) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (22) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. (23) Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck and Tyrolean Cancer Research Institute, Medical University of Innsbruck, Innsbruck, Austria. (24) Institute for Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria. gottfried.baier@i-med.ac.at.

Citation: Nat Commun 2026 Feb 27 Epub02/27/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41760655

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Erythrocyte-anti-PD1 conjugates in persons with advanced solid tumors resistant to anti-PD1/PDL1: preclinical characterization and results of a phase 1 trial Spotlight 

(1) Nie X (2) Liu Y (3) Yao X (4) Zhang Q (5) Huang Y (6) Mattursun K (7) Feng Y (8) Liang T (9) Yang L (10) Gao X

Nature cancer

Nie, Liu, Yao, et al. developed an erythrocyte–antibody conjugate in which anti-PD-1 antibodies were covalently linked to erythrocyte membranes (αPD1-Ery). These cellular-Ab conjugates accumulated in spleens, where they expanded effector T cells and reduced immunosuppressive myeloid cells, leading to reduced tumor growth in mouse models. In a first-in-human phase I clinical trial, 14 patients with advanced cancers who were resistant to anti-PD-1/L1 were treated at 2 dose levels, which were well tolerated and reduced circulating immunosuppressive myeloid cells. The ORR was 42.9%, with 1 CR and 5 PRs, and the DCR was 78.6%.

Contributed by Lauren Hitchings

(1) Nie X (2) Liu Y (3) Yao X (4) Zhang Q (5) Huang Y (6) Mattursun K (7) Feng Y (8) Liang T (9) Yang L (10) Gao X

Nature cancer

Nie, Liu, Yao, et al. developed an erythrocyte–antibody conjugate in which anti-PD-1 antibodies were covalently linked to erythrocyte membranes (αPD1-Ery). These cellular-Ab conjugates accumulated in spleens, where they expanded effector T cells and reduced immunosuppressive myeloid cells, leading to reduced tumor growth in mouse models. In a first-in-human phase I clinical trial, 14 patients with advanced cancers who were resistant to anti-PD-1/L1 were treated at 2 dose levels, which were well tolerated and reduced circulating immunosuppressive myeloid cells. The ORR was 42.9%, with 1 CR and 5 PRs, and the DCR was 78.6%.

Contributed by Lauren Hitchings

ABSTRACT: Despite the clinical success of immune checkpoint blockade therapy, most persons do not benefit because of inadequate efficacy, primary or acquired resistance and/or immune-related toxicities. Here we developed an erythrocyte-antibody conjugate in which anti-PD1 antibodies are covalently linked to erythrocyte membranes (αPD1-Ery). Unlike conventional antibodies, αPD1-Ery accumulates in the spleen, where it remodels the immune landscape by expanding effector T cells and reducing immunosuppressive myeloid cells. These changes reprogram the tumor microenvironment and suppress tumor growth in syngeneic mouse models. We conducted a first-in-human, phase 1 clinical trial of αPD1-Ery monotherapy in persons with advanced cancers resistant to prior anti-PD1/PDL1 therapy ( NCT06026605 ). The primary objective was safety; secondary objectives included efficacy, pharmacokinetics, pharmacodynamics and immunogenicity. A total of 14 participants were enrolled, with 7 receiving 2 × 1011 cells and 7 receiving 3 × 1011 cells. Repeated administration resulted in no dose-limiting toxicities or treatment-related adverse events of grade >3. The objective response rate was 42.9%, including 1 complete response and 5 partial responses; disease control rate was 78.6%. Notably, αPD1-Ery rapidly reduced circulating immunosuppressive myeloid cells, consistent with preclinical observations. The study met its prespecified primary and secondary endpoints. These findings support spleen-targeted PD1 blockade by erythrocyte-antibody conjugates as a potential strategy for cancer immunotherapy.

Author Info: (1) School of Basic Medical Sciences, Fudan University, Shanghai, China. Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Science

Author Info: (1) School of Basic Medical Sciences, Fudan University, Shanghai, China. Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China. (2) Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China. (3) Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China. (4) The Key Laboratory of Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (5) School of Basic Medical Sciences, Fudan University, Shanghai, China. Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China. (6) Westlake Therapeutics, Hangzhou, China. (7) Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China. yxfeng@zju.edu.cn. Cancer Center, Zhejiang University, Hangzhou, China. yxfeng@zju.edu.cn. (8) The Key Laboratory of Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. liangtingbo@zju.edu.cn. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. liangtingbo@zju.edu.cn. (9) Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, China. yangliu@hmc.edu.cn. (10) Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. gaoxiaofei@westlake.edu.cn. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. gaoxiaofei@westlake.edu.cn. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China. gaoxiaofei@westlake.edu.cn. Research Center for Industries of the Future and School of Engineering, Westlake University, Hangzhou, China. gaoxiaofei@westlake.edu.cn.

Citation: Nat Cancer 2026 Feb 20 Epub02/20/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41721136

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Engineered CCR7 overexpression enhances nodal CAR-T cell homing and cytotoxicity toward B cell lymphoma Spotlight 

(1) Zschummel M (2) Bunse M (3) Spierling AL (4) Li A (5) Joedicke JJ (6) Margineanu A (7) Blachut S (8) Lindberg EL (9) Ruiz-Orera J (10) Hübner N (11) Rehm A (12) Höpken UE

Cancer immunology research

Finding that CCR7 was downregulated during CAR T manufacturing, Zschummel et al. generated CAR T cells with CCR7 overexpression (CAR.CCR7). Compared to CAR-T, CAR.CCR7-T had increased CCL19-mediated migration in vitro, and demonstrated LN accumulation and lymphoma depletion in a syngeneic mouse model. CAR.CCR7-T had superior cytotoxicity in vitro compared to standard CAR-T, especially at low E:T, but not due to CAR or Th1 cytokine expression, or the ligand CCL19. CAR.CCR7-T cells were larger, had increased cytoskeletal regulatory gene expression, recruited CCR7 to the immune synapse, and showed early ZAP70 phosphorylation and degranulation.

Contributed by Alex Najibi

(1) Zschummel M (2) Bunse M (3) Spierling AL (4) Li A (5) Joedicke JJ (6) Margineanu A (7) Blachut S (8) Lindberg EL (9) Ruiz-Orera J (10) Hübner N (11) Rehm A (12) Höpken UE

Cancer immunology research

Finding that CCR7 was downregulated during CAR T manufacturing, Zschummel et al. generated CAR T cells with CCR7 overexpression (CAR.CCR7). Compared to CAR-T, CAR.CCR7-T had increased CCL19-mediated migration in vitro, and demonstrated LN accumulation and lymphoma depletion in a syngeneic mouse model. CAR.CCR7-T had superior cytotoxicity in vitro compared to standard CAR-T, especially at low E:T, but not due to CAR or Th1 cytokine expression, or the ligand CCL19. CAR.CCR7-T cells were larger, had increased cytoskeletal regulatory gene expression, recruited CCR7 to the immune synapse, and showed early ZAP70 phosphorylation and degranulation.

Contributed by Alex Najibi

ABSTRACT: Anti-CD19 chimeric antigen receptor (CAR) therapy demonstrated remarkable efficacy against hematological malignancies. However, B cell malignancies with lymph node (LN) involvement frequently remain resistant. Here, we show that CAR T cells downregulated the chemokine receptor CCR7, crucial for nodal homing, during manufacturing. Consequently, in vitro migration toward the respective chemokines and in vivo migration to LNs was severely impaired. To improve nodal CAR T-cell trafficking, we engineered anti-CXCR5 CAR T cells, targeting mature lymphoma, with stable CCR7 expression (CAR.CCR7). CCR7 engineering of human and mouse CAR T cells restored migratory capacity and LN homing. Additionally, we observed enhanced CAR-mediated killing in CCR7-engineered anti-CXCR5 and anti-CD19-CARs alike, a process that was independent of increased cytokine secretion. Mechanistically, CCR7 overexpression was associated with an altered expression of genes involved in cytoskeletal rearrangement and faster killing kinetics. CCR7 accumulated in mature CAR synapses, supporting the costimulatory role of CCR7 within immunological synapses. Therapeutically, improved LN-recruitment and enhanced killing of CAR.CCR7 T cells improved lymphoma eradication in mice.

Author Info: (1) Massachusetts General Hospital Charlestown, Massachusetts United States. ROR: https://ror.org/002pd6e78 (2) Max DelbrŸck Center for Molecular Medicine Berlin, Berlin Germany. R

Author Info: (1) Massachusetts General Hospital Charlestown, Massachusetts United States. ROR: https://ror.org/002pd6e78 (2) Max DelbrŸck Center for Molecular Medicine Berlin, Berlin Germany. ROR: https://ror.org/04p5ggc03 (3) Max DelbrŸck Center for Molecular Medicine Berlin Germany. ROR: https://ror.org/04p5ggc03 (4) Max DelbrŸck Center Berlin, Berlin Germany. (5) Max DelbrŸck Center for Molecular Medicine Berlin Germany. ROR: https://ror.org/04p5ggc03 (6) Max DelbrŸck Center for Molecular Medicine Berlin Germany. ROR: https://ror.org/04p5ggc03 (7) Max DelbrŸck Center for Molecular Medicine Berlin Germany. (8) Max DelbrŸck Center for Molecular Medicine Berlin Germany. (9) Max DelbrŸck Center for Molecular Medicine Berlin Germany. (10) Max DelbrŸck Center for Molecular Medicine Berlin Germany. (11) Max DelbrŸck Center for Molecular Medicine Berlin Germany. ROR: https://ror.org/04p5ggc03 (12) Max DelbrŸck Center for Molecular Medicine Berlin Germany. ROR: https://ror.org/04p5ggc03

Citation: Cancer Immunol Res 2026 Feb 24 Epub02/24/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41733597

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Metabolic quiescence of naive-like memory T cells precedes and maintains antigen-specific T cell memory Spotlight 

(1) Frischholz S (2) Schuster EM (3) Grotz M (4) Schülein C (5) Benz J (6) Kocher K (7) Klotz L (8) Varga S (9) Hiltner T (10) Alsalameh R (11) Esse J (12) Träger J (13) Held J (14) Graw F (15) Pahle J (16) Spriewald B (17) Gattinoni L (18) Buchholz VR (19) Drost F (20) Schubert B (21) RothenfuBer S (22) Busch DH (23) Bogdan C (24) Schober K

Nature immunology | Free PMC Article

Frischholz et al. analyzed CD8+ T cells after yellow fever vaccination, and found that TEM and TCM phenotypes dominated the acute response at 14 days. However, a naive-like T memory population (TNM) comprised ~50% of the repertoire at 1 year, and remained for decades post-vaccination. At 14 days, TNM were characterized by quiescence, downregulated effector programs, low proliferation, and minimal apoptosis. This was in contrast to TCM, cycling, and effector-like populations, which contracted within 1-2 months. While all T cells primarily leveraged oxidative phosphorylation, TCM uniquely leveraged glycolysis, and TNM exclusively utilized OXPHOS.

Contributed by Morgan Janes

(1) Frischholz S (2) Schuster EM (3) Grotz M (4) Schülein C (5) Benz J (6) Kocher K (7) Klotz L (8) Varga S (9) Hiltner T (10) Alsalameh R (11) Esse J (12) Träger J (13) Held J (14) Graw F (15) Pahle J (16) Spriewald B (17) Gattinoni L (18) Buchholz VR (19) Drost F (20) Schubert B (21) RothenfuBer S (22) Busch DH (23) Bogdan C (24) Schober K

Nature immunology | Free PMC Article

Frischholz et al. analyzed CD8+ T cells after yellow fever vaccination, and found that TEM and TCM phenotypes dominated the acute response at 14 days. However, a naive-like T memory population (TNM) comprised ~50% of the repertoire at 1 year, and remained for decades post-vaccination. At 14 days, TNM were characterized by quiescence, downregulated effector programs, low proliferation, and minimal apoptosis. This was in contrast to TCM, cycling, and effector-like populations, which contracted within 1-2 months. While all T cells primarily leveraged oxidative phosphorylation, TCM uniquely leveraged glycolysis, and TNM exclusively utilized OXPHOS.

Contributed by Morgan Janes

ABSTRACT: Metabolic activity shapes cell fate but remains challenging to capture in vivo with high resolution. Here we performed longitudinal metabolic and phenotypic profiling of human antigen-specific CD8(+) T cells after yellow fever vaccination using flow cytometry and single-cell RNA sequencing. As assessed by protein translation rates, CD8(+) T cells upregulated glycolysis to fuel anabolic needs for proliferation but predominantly used oxidative phosphorylation for energy production during the acute phase (days 7-28) after vaccination. Simultaneously, CD8(+)CD62L(+)CD45RA(-) central memory T cells were the most metabolically active subset, whereas CD8(+)CD62L(-)CD45RA(+) effector T cells underwent metabolic shutdown. Weakly differentiated CD8(+)CD62L(+)CD45RA(+)CD95(-) naive-like memory T cells showed minimal activity, relied solely on oxidative phosphorylation and were preferentially maintained 26 years postvaccination, reinforcing the link between cellular quiescence and longevity. Our study highlights quiescence as a key feature for long-term immunological memory formation in humans.

Author Info: (1) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany

Author Info: (1) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (2) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (3) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (4) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (5) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (6) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (7) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (8) Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg (FAU) and UniversitŠtsklinikum Erlangen, Erlangen, Germany. Biological Information Processing Group, BioQuant, Heidelberg University, Heidelberg, Germany. (9) Institute for Medical Microbiology, Immunology, and Hygiene, School of Medicine and Health, Technical University of Munich, Munich, Germany. (10) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (11) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (12) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (13) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. (14) Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg (FAU) and UniversitŠtsklinikum Erlangen, Erlangen, Germany. Deutsches Zentrum Immuntherapie, FAU Erlangen-NŸrnberg and UniversitŠtsklinikum Erlangen, Erlangen, Germany. (15) Biological Information Processing Group, BioQuant, Heidelberg University, Heidelberg, Germany. (16) Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg (FAU) and UniversitŠtsklinikum Erlangen, Erlangen, Germany. (17) Division of Functional Immune Cell Modulation, Leibniz Institute for Immunotherapy, Regensburg, Germany. University of Regensburg, Regensburg, Germany. Center for Immunomedicine in Transplantation and Oncology, University Hospital Regensburg, Regensburg, Germany. (18) Institute for Medical Microbiology, Immunology, and Hygiene, School of Medicine and Health, Technical University of Munich, Munich, Germany. Division of Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. (19) Institute of Computational Biology, Helmholtz Zentrum MŸnchen - German Research Center for Environmental Health, Neuherberg, Germany. (20) Institute of Computational Biology, Helmholtz Zentrum MŸnchen - German Research Center for Environmental Health, Neuherberg, Germany. (21) Institute of Clinical Pharmacology, LMU University Hospital, LMU Munich, Munich, Germany. Einheit fŸr Klinische Pharmakologie (EKLiP), Helmholtz Zentrum MŸnchen German Research Center for Environmental Health (HMGU), Neuherberg, Germany. (22) Institute for Medical Microbiology, Immunology, and Hygiene, School of Medicine and Health, Technical University of Munich, Munich, Germany. German Center for Infection Research, Partner Site Munich, Munich, Germany. (23) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. FAU Profile Center Immunomedicine, FAU Erlangen-NŸrnberg, Erlangen, Germany. (24) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, UniversitŠtsklinikum Erlangen, Friedrich-Alexander-UniversitŠt Erlangen-NŸrnberg, Erlangen, Germany. kilian.schober@uk-erlangen.de. FAU Profile Center Immunomedicine, FAU Erlangen-NŸrnberg, Erlangen, Germany. kilian.schober@uk-erlangen.de.

Citation: Nat Immunol 2026 Mar 27:452-462 Epub02/24/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41735532

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Sensitive CAR T cells redefine targetable CD70 expression in solid tumors Spotlight 

(1) Hanina SA (2) Park T (3) Lopez M (4) Rajasekhar VK (5) Mansilla-Soto J (6) Haubner S (7) Zhao H (8) Kogel F (9) Nataraj S (10) Banerjee P (11) Koche R (12) Hamard PJ (13) Tarcan ZC (14) Chi DS (15) Zamarin D (16) Healey JH (17) de Stanchina E (18) Motzer RJ (19) Kotecha RR (20) Hakimi AA (21) Leslie CS (22) Sadelain M

Science

Hanina et al. demonstrated that CD70 is heterogeneously expressed in solid tumors ranging to ultra-low, due to epigenetic silencing of CD70 by EZH2-mediated H3K27 trimethylation. Conventional detection assays were unable to detect ultra-low levels of CD70, and commonly used CARs failed to achieve complete tumor clearance. A more sensitive CD70-targeted CAR T cell utilizing a VH/VL-engineered HLA-independent T cell receptor (HIT) eradicated heterogeneous tumors, without additional toxicity, in xenograft models of multiple cancers. An epigenetic signature based on CD70 chromatin accessibility detected ultra-low expression and HIT sensitivity.

Contributed by Shishir Pant

(1) Hanina SA (2) Park T (3) Lopez M (4) Rajasekhar VK (5) Mansilla-Soto J (6) Haubner S (7) Zhao H (8) Kogel F (9) Nataraj S (10) Banerjee P (11) Koche R (12) Hamard PJ (13) Tarcan ZC (14) Chi DS (15) Zamarin D (16) Healey JH (17) de Stanchina E (18) Motzer RJ (19) Kotecha RR (20) Hakimi AA (21) Leslie CS (22) Sadelain M

Science

Hanina et al. demonstrated that CD70 is heterogeneously expressed in solid tumors ranging to ultra-low, due to epigenetic silencing of CD70 by EZH2-mediated H3K27 trimethylation. Conventional detection assays were unable to detect ultra-low levels of CD70, and commonly used CARs failed to achieve complete tumor clearance. A more sensitive CD70-targeted CAR T cell utilizing a VH/VL-engineered HLA-independent T cell receptor (HIT) eradicated heterogeneous tumors, without additional toxicity, in xenograft models of multiple cancers. An epigenetic signature based on CD70 chromatin accessibility detected ultra-low expression and HIT sensitivity.

Contributed by Shishir Pant

ABSTRACT: Solid tumor antigen heterogeneity is a major challenge for cancer immunotherapies, including chimeric antigen receptor (CAR) T cells. Unlike CD19 for B cell malignancies, no target with pan-cellular expression in solid tumors and absence in normal vital cells has been identified. CD70 is a promising candidate, physiologically confined to immune cell subsets and aberrantly expressed in many cancers. We show that heterogeneous CD70 expression in tumors is epigenetically regulated, ranging from high to very low in individual cells, appearing negative by conventional detection methods. Using a highly sensitive CD70 receptor, HLA-independent T cell (HIT) receptor coexpressing CD80 and 4-1BBL for costimulation, we efficiently eliminated CD70-heterogeneous tumors that evade prototypic CAR T cells. These findings provide a potential strategy to treat a broad range of solid tumors.

Author Info: (1) Columbia Initiative in Cell Engineering and Therapy (CICET), Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY USA. (2) Compu

Author Info: (1) Columbia Initiative in Cell Engineering and Therapy (CICET), Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY USA. (2) Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (3) Columbia Initiative in Cell Engineering and Therapy (CICET), Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY USA. (4) Orthopedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (5) Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (6) Columbia Initiative in Cell Engineering and Therapy (CICET), Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY USA. (7) Antitumor Assessment Core Facility, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (8) Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (9) Columbia Initiative in Cell Engineering and Therapy (CICET), Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY USA. (10) Bio-Imaging Resource Center, The Rockefeller University, New York, NY USA. (11) Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (12) Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (13) Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (14) Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA. (15) Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (16) Orthopedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (17) Antitumor Assessment Core Facility, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (18) Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (19) Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (20) Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (21) Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (22) Columbia Initiative in Cell Engineering and Therapy (CICET), Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY USA.

Citation: Science 2026 Feb 26 391:896-905 Epub02/26/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41747043

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Tumor-associated CD19+ macrophages induce immunosuppressive microenvironment in hepatocellular carcinoma

Spotlight 

(1) Wang J (2) Cao W (3) Huang J (4) Zhou Y (5) Zheng R (6) Lou Y (7) Yang J (8) Yan J (9) Tang J (10) Ye M (11) Hong Z (12) Wu J (13) Ding H (14) Zhang Y (15) Sheng J (16) Lu X (17) Xu P (18) Lu X (19) Bai X (20) Liang T (21) Zhang Q

Nature communications

Wang and Cao et al. focused on how TAMs contribute to tumor progression. An immunosuppressive CD19+ macrophage subpopulation, associated with poor clinical outcomes, was enriched in HCC and many other cancer types. These cells exhibited increased levels of PD-L1 and CD73, enhanced mitochondrial oxidation, and deficient phagocytosis. Mechanistically, PAX5 drove mitochondrial biogenesis in CD19+ TAMs, depleting cytosolic Ca2+, leading to lysosomal deficiency and accumulation of PD-L1 and CD73. Targeting CD19+ TAMs with CD19-specific CAR T cells, anti-CD73, or OXPHOS inhibitors enhanced the efficacy of checkpoint blockade therapy in HCC models.

Contributed by Katherine Turner

(1) Wang J (2) Cao W (3) Huang J (4) Zhou Y (5) Zheng R (6) Lou Y (7) Yang J (8) Yan J (9) Tang J (10) Ye M (11) Hong Z (12) Wu J (13) Ding H (14) Zhang Y (15) Sheng J (16) Lu X (17) Xu P (18) Lu X (19) Bai X (20) Liang T (21) Zhang Q

Nature communications

Wang and Cao et al. focused on how TAMs contribute to tumor progression. An immunosuppressive CD19+ macrophage subpopulation, associated with poor clinical outcomes, was enriched in HCC and many other cancer types. These cells exhibited increased levels of PD-L1 and CD73, enhanced mitochondrial oxidation, and deficient phagocytosis. Mechanistically, PAX5 drove mitochondrial biogenesis in CD19+ TAMs, depleting cytosolic Ca2+, leading to lysosomal deficiency and accumulation of PD-L1 and CD73. Targeting CD19+ TAMs with CD19-specific CAR T cells, anti-CD73, or OXPHOS inhibitors enhanced the efficacy of checkpoint blockade therapy in HCC models.

Contributed by Katherine Turner

ABSTRACT: Tumor-associated macrophages are a key component that contributes to the immunosuppressive microenvironment in human cancers. However, therapeutic targeting of macrophages has been a challenge in clinic due to the limited understanding of their heterogeneous subpopulations and distinct functions. Here, we identify a clinically relevant CD19(+) subpopulation of macrophages that is enriched in many types of cancer, particularly in hepatocellular carcinoma (HCC). The CD19(+) macrophages exhibit increased levels of programmed cell death 1 ligand 1 (PD-L1) and CD73, enhanced mitochondrial oxidation, and compromised phagocytosis, indicating their immunosuppressive functions. Targeting CD19(+) macrophages with anti-CD19 chimeric antigen receptor T (CAR-T) cells inhibited HCC tumor growth. We identify Paired Box 5 (PAX5) as a primary driver of up-regulated mitochondrial biogenesis in CD19(+) macrophages, which depletes cytoplasmic Ca(2+), leading to lysosomal deficiency and consequent accumulation of CD73 and PD-L1. Inhibiting CD73 or mitochondrial oxidation enhanced the efficacy of immune checkpoint blockade therapy in treating HCC, suggesting great promise for CD19(+) macrophage-targeting therapeutics.

Author Info: (1) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory o

Author Info: (1) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (2) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (3) Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Biomedical Big Data Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (4) Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (5) Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Biomedical Big Data Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (6) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (7) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (8) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (9) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (10) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (11) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (12) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (13) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (14) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (15) Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang University Cancer Center, Hangzhou, China. MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou, China. (16) Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China. (17) Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang University Cancer Center, Hangzhou, China. Life Sciences Institute, Zhejiang University, Hangzhou, China. (18) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (19) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Zhejiang University Cancer Center, Hangzhou, China. MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou, China. Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, Zhejiang, China. The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. (20) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. liangtingbo@zju.edu.cn. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. liangtingbo@zju.edu.cn. Zhejiang University Cancer Center, Hangzhou, China. liangtingbo@zju.edu.cn. MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou, China. liangtingbo@zju.edu.cn. Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, Zhejiang, China. liangtingbo@zju.edu.cn. The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. liangtingbo@zju.edu.cn. (21) Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. qi.zhang@zju.edu.cn. Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. qi.zhang@zju.edu.cn. Zhejiang University Cancer Center, Hangzhou, China. qi.zhang@zju.edu.cn. MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou, China. qi.zhang@zju.edu.cn. Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, Zhejiang, China. qi.zhang@zju.edu.cn. The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. qi.zhang@zju.edu.cn.

Citation: Nat Commun 2026 Feb 26 Epub02/26/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41748561

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Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC Featured  

(1) Sahin U (2) Schmidt M (3) Derhovanessian E (4) Cortini A (5) Vogler I (6) Omokoko T (7) Godehardt E (8) Attig S (9) Newrzela S (10) Grützner J (11) Bidmon N (12) Bolte S (13) Brachtendorf S (14) Stuhlmann T (15) Langer D (16) Brüne D (17) Blake J (18) Feldner A (19) Lindman H (20) Schneeweiss A (21) Eichbaum M (22) Türeci O

Nature

Sahin, Schmidt, et al. conducted a clinical study of patients with early-stage TNBC who were treated with a personalized neoantigen mRNA vaccine strategy following standard therapy. Durable neoantigen-specific CD8+ and CD4+ T cell responses were detected, with 10/14 patients remaining relapse-free during long-term follow-up. Several resistance mechanisms were uncovered in three patients with recurrences; a weak vaccine-induced response, recurrence related to the primary tumor not used for vaccine creation, and downregulation of antigen presentation in tumor cells.

(1) Sahin U (2) Schmidt M (3) Derhovanessian E (4) Cortini A (5) Vogler I (6) Omokoko T (7) Godehardt E (8) Attig S (9) Newrzela S (10) Grützner J (11) Bidmon N (12) Bolte S (13) Brachtendorf S (14) Stuhlmann T (15) Langer D (16) Brüne D (17) Blake J (18) Feldner A (19) Lindman H (20) Schneeweiss A (21) Eichbaum M (22) Türeci O

Nature

Sahin, Schmidt, et al. conducted a clinical study of patients with early-stage TNBC who were treated with a personalized neoantigen mRNA vaccine strategy following standard therapy. Durable neoantigen-specific CD8+ and CD4+ T cell responses were detected, with 10/14 patients remaining relapse-free during long-term follow-up. Several resistance mechanisms were uncovered in three patients with recurrences; a weak vaccine-induced response, recurrence related to the primary tumor not used for vaccine creation, and downregulation of antigen presentation in tumor cells.

ABSTRACT: Triple-negative breast cancer (TNBC) is frequently associated with metastatic relapse, even at an early stage(1). Here we assessed an individualized neoantigen mRNA vaccine in 14 patients with TNBC following surgery and after neoadjuvant or adjuvant therapy. In peripheral blood of nearly all patients, high-magnitude, vaccine-induced, mostly de novo T cell responses to multiple neoantigens were detected that remained functional for several years. Characterization of individual patients revealed that a large proportion of these T cells developed into two subsets: a late-differentiated phenotype with markers indicative of 'ready-to-act' cytotoxic effector T cells, and T cells with a stem cell-like memory phenotype. Eleven patients remained relapse-free for up to six years post-vaccination. Recurrence occurred in three patients: the individual with the weakest vaccine-induced T cell response relapsed, but achieved complete remission on subsequent anti-PD-1 therapy; another patient had a tumour with low major histocompatibility complex (MHC) class I expression with MHC class I-deficient cells growing out under vaccination; and the third patient was BRCA-positive and had a recurrence from a genetically distinct primary tumour. These findings demonstrate the feasibility of individualized RNA vaccines in TNBC, document persistence of vaccine-induced, functional neoantigen-specific T cells and provide insights into possible immune escape mechanisms that will guide future approaches.

Author Info: (1) BioNTech Group, Mainz, Germany. ugur.sahin@biontech.de. TRON, Mainz, Germany. ugur.sahin@biontech.de. HI-TRON Mainz, Mainz, Germany. ugur.sahin@biontech.de. (2) Department of O

Author Info: (1) BioNTech Group, Mainz, Germany. ugur.sahin@biontech.de. TRON, Mainz, Germany. ugur.sahin@biontech.de. HI-TRON Mainz, Mainz, Germany. ugur.sahin@biontech.de. (2) Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. (3) BioNTech Group, Mainz, Germany. (4) BioNTech Group, Mainz, Germany. (5) BioNTech Group, Mainz, Germany. (6) BioNTech Group, Mainz, Germany. (7) BioNTech Group, Mainz, Germany. (8) TRON, Mainz, Germany. (9) BioNTech Group, Mainz, Germany. (10) BioNTech Group, Mainz, Germany. (11) BioNTech Group, Mainz, Germany. (12) BioNTech Group, Mainz, Germany. (13) BioNTech Group, Mainz, Germany. (14) BioNTech Group, Mainz, Germany. (15) BioNTech Group, Mainz, Germany. (16) BioNTech Group, Mainz, Germany. (17) BioNTech Group, Mainz, Germany. (18) BioNTech Group, Mainz, Germany. (19) Department of Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden. (20) Division Gynecologic Oncology, National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany. (21) Klinik fŸr Frauenheilkunde und Geburtshilfe, Helios Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany. (22) BioNTech Group, Mainz, Germany. HI-TRON Mainz, Mainz, Germany.

Citation: Nature 2026 Feb 18 Epub02/18/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41708868

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16-h fasting optimizes cancer immunotherapy in mice and humans Spotlight 

(1) Chen S (2) Hu T (3) Zhu K (4) Liu Y (5) Yang Y (6) Li X (7) He J (8) Cui W (9) Chi Z (10) Yu W (11) Chen D (12) Wang Z (13) Zhang J (14) Sun R (15) Yang D (16) Dai S (17) Yu Q (18) Wang Q (19) Xiao Q (20) Qian J (21) Ding K (22) Wang D

Cell metabolism

Chen et al. designed an overnight 16h fasting regimen that augmented ICB efficacy in mice and patients with colorectal cancer. Fasting reprogrammed tumor cell nutrient preferences, triggering a metabolic trade-off that enriched intratumoral isoleucine (Ile). Ile fueled the acetyl-CoA pool in CD8+ T cells, which coordinated the epigenetic landscape and membrane lipid dynamics required for CD8+ T cell effector functions. Fasting reduced exhausted T cell populations, increased TEMRA and TRM effector functions, augmented the clonal expansion and cytotoxic activity of CD8+ T cells, and enhanced anti-PD-1 efficacy in preclinical models and patients with CRC.

Contributed by Shishir Pant

(1) Chen S (2) Hu T (3) Zhu K (4) Liu Y (5) Yang Y (6) Li X (7) He J (8) Cui W (9) Chi Z (10) Yu W (11) Chen D (12) Wang Z (13) Zhang J (14) Sun R (15) Yang D (16) Dai S (17) Yu Q (18) Wang Q (19) Xiao Q (20) Qian J (21) Ding K (22) Wang D

Cell metabolism

Chen et al. designed an overnight 16h fasting regimen that augmented ICB efficacy in mice and patients with colorectal cancer. Fasting reprogrammed tumor cell nutrient preferences, triggering a metabolic trade-off that enriched intratumoral isoleucine (Ile). Ile fueled the acetyl-CoA pool in CD8+ T cells, which coordinated the epigenetic landscape and membrane lipid dynamics required for CD8+ T cell effector functions. Fasting reduced exhausted T cell populations, increased TEMRA and TRM effector functions, augmented the clonal expansion and cytotoxic activity of CD8+ T cells, and enhanced anti-PD-1 efficacy in preclinical models and patients with CRC.

Contributed by Shishir Pant

ABSTRACT: Dietary interventions hold promise for cancer therapy but often require prolonged, poorly tolerated regimens. Furthermore, how transient nutrient deprivation affects the metabolic interplay between tumor and immune cells within the tumor microenvironment (TME) remains unknown. Here, we introduce a brief, 16-h fasting regimen that enhances immunotherapy efficacy in both mice and humans. We found that this transient nutrient stress alters tumor-cell nutrient preferences, creating a metabolic window that can be leveraged to augment treatment. Mechanistically, short-term fasting induces intratumoral accumulation of isoleucine, which reconfigures CD8(+) T cell epigenetic programs and phospholipid remodeling, thereby licensing enhanced anti-tumor capacity. In patients receiving neoadjuvant immunotherapy, short-term fasting was able to enhance CD8(+) clonal expansion and cytotoxic programs. These findings establish a clinically feasible, well-tolerated dietary regimen that counters nutrient competition in the TME and that provides a tractable path to strengthen existing immunotherapy regimens.

Author Info: (1) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University

Author Info: (1) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (2) Institute of Immunology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (3) Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China. (4) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (5) Institute of Immunology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (6) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (7) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (8) Eye Center, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (9) Center for Regeneration and Aging Medicine, The Fourth Affiliated Hospital of School of Medicine, International School of Medicine, International Institutes of Medicine, Yiwu 322000, P.R. China. (10) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (11) Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China; Institute of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (12) Institute of Immunology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (13) Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311113, P.R. China. (14) Institute of Immunology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (15) Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311113, P.R. China. (16) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (17) Institute of Immunology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (18) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (19) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China. (20) Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China; Institute of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. (21) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Cancer Center, Zhejiang University, Hangzhou 310058, P.R. China; Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Hangzhou 310020, P.R. China; Zhejiang Provincial Clinical Research Center for CANCER, Hangzhou 310009, P.R. China. Electronic address: dingkefeng@zju.edu.cn. (22) Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310017, P.R. China; Institute of Immunology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311113, P.R. China; Zhejiang Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. Electronic address: diwang@zju.edu.cn.

Citation: Cell Metab 2026 Feb 19 Epub02/19/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41720105

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Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8+ T cells in lymph nodes

Featured  

(1) Lai J (2) Chan CW (3) Armitage JD (4) Audsley KM (5) Huang YK (6) Derrick EB (7) Carstensen LS (8) Scheffler CM (9) Jones ME (10) Sek K (11) Principe N (12) Kim JS (13) House IG (14) Chen AXY (15) Yap KM (16) Middelburg J (17) Munoz I (18) Nguyen D (19) Tong J (20) Hoang TX (21) Todd KL (22) Evrard M (23) Chee J (24) Mackay LK (25) Forrest ARR (26) Parish IA (27) Bosco A (28) Waithman J (29) Beavis PA (30) Darcy PK

Nature immunology

Lai, Chan, Armitage, et al. investigated whether Flt3L treatment could improve immune checkpoint blockade responses. Flt3L increased cDC1 and stem-like precursor exhausted T cells (Tpex) populations through enhanced priming in the draining lymph nodes. Combining Flt3L treatment with CTLA-4 blockade resulted in expansion of stem-like and tumor antigen-specific effector T cell populations in the tumor, resulting in improved outcomes in mouse models.

(1) Lai J (2) Chan CW (3) Armitage JD (4) Audsley KM (5) Huang YK (6) Derrick EB (7) Carstensen LS (8) Scheffler CM (9) Jones ME (10) Sek K (11) Principe N (12) Kim JS (13) House IG (14) Chen AXY (15) Yap KM (16) Middelburg J (17) Munoz I (18) Nguyen D (19) Tong J (20) Hoang TX (21) Todd KL (22) Evrard M (23) Chee J (24) Mackay LK (25) Forrest ARR (26) Parish IA (27) Bosco A (28) Waithman J (29) Beavis PA (30) Darcy PK

Nature immunology

Lai, Chan, Armitage, et al. investigated whether Flt3L treatment could improve immune checkpoint blockade responses. Flt3L increased cDC1 and stem-like precursor exhausted T cells (Tpex) populations through enhanced priming in the draining lymph nodes. Combining Flt3L treatment with CTLA-4 blockade resulted in expansion of stem-like and tumor antigen-specific effector T cell populations in the tumor, resulting in improved outcomes in mouse models.

ABSTRACT: Immune checkpoint blockade (ICB) evokes antitumor immunity through the reinvigoration of T cell responses. T cell differentiation status controls response, with less differentiated cells having an enhanced capacity to proliferate after ICB. Given that conventional type 1 dendritic cells (cDC1) maintain precursor exhausted T cells (TPEX), we hypothesized that expansion of cDC1s with Flt3L could enhance responses to ICB. Here we show that treatment with Fms-related tyrosine kinase 3 ligand (Flt3L) expands CD62L+SLAMF6+CD8+ T cells in the tumor through a mechanism that requires XCR1+ dendritic cells to traffic to the tumor-draining lymph node. The combination of Flt3L and anti-CTLA-4 enhanced therapeutic responses. Combination therapy is associated with the emergence of a CD8+ T cell subset characterized by the expression of Il21r and oligoclonal expansion of CD8+ T cells within tumors through a mechanism that is dependent on lymph node egress.

Author Info: (1) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Vi

Author Info: (1) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (2) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (3) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia. The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia. (4) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (5) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (6) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (7) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (8) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (9) Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia. (10) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (11) Institute for Respiratory Health, National Centre for Asbestos Related Diseases, The University of Western Australia, Perth, Western Australia, Australia. (12) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (13) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (14) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (15) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (16) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (17) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (18) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (19) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (20) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (21) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (22) Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia. (23) Institute for Respiratory Health, National Centre for Asbestos Related Diseases, The University of Western Australia, Perth, Western Australia, Australia. (24) Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia. (25) Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia. (26) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. (27) Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, USA. Department of Immunobiology, The University of Arizona College of Medicine, Tucson, AZ, USA. (28) School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia. jason.waithman@uwa.edu.au. (29) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. paul.beavis@petermac.org. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. paul.beavis@petermac.org. (30) Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. phil.darcy@petermac.org. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. phil.darcy@petermac.org. Department of Immunology, Monash University, Clayton, Victoria, Australia. phil.darcy@petermac.org.

Citation: Nat Immunol 2026 Feb 10 Epub02/10/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41667622

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Ex vivo expansion of melanoma tumor infiltrating lymphocytes leads to a dominant exhausted T cell population with lack of memory markers Spotlight 

(1) Coppola G (2) Kerr S (3) Cha PC (4) Bersenev A (5) Olino K (6) Kluger HM (7) Sznol M (8) Weiss SA (9) Bosenberg MW (10) Kleinstein SH (11) Krause DS (12) Hurwitz ME (13) Katz SG

Cancer immunology research

Using scRNA- and scTCRseq profiling, Coppola and Kerr et al. showed that large changes were induced during ex vivo expansion of TIL samples from six patients with metastatic melanoma. Post-expansion TILs lacked naive or memory cells, and were primarily exhausted, exhibiting decreased expression of PD-1, 4-1BB, and CD27, and increased expression of TIM3, LAG3, CD30, and cytotoxicity- and APC-associated genes. Although terminally differentiated, the expanded TILs contained a large progenitor exhausted CD8+ T cell population and increased absolute numbers of CD39/CD69 double-negative "stem-like" T cells, previously implicated for TIL efficacy.

Contributed by Paula Hochman

(1) Coppola G (2) Kerr S (3) Cha PC (4) Bersenev A (5) Olino K (6) Kluger HM (7) Sznol M (8) Weiss SA (9) Bosenberg MW (10) Kleinstein SH (11) Krause DS (12) Hurwitz ME (13) Katz SG

Cancer immunology research

Using scRNA- and scTCRseq profiling, Coppola and Kerr et al. showed that large changes were induced during ex vivo expansion of TIL samples from six patients with metastatic melanoma. Post-expansion TILs lacked naive or memory cells, and were primarily exhausted, exhibiting decreased expression of PD-1, 4-1BB, and CD27, and increased expression of TIM3, LAG3, CD30, and cytotoxicity- and APC-associated genes. Although terminally differentiated, the expanded TILs contained a large progenitor exhausted CD8+ T cell population and increased absolute numbers of CD39/CD69 double-negative "stem-like" T cells, previously implicated for TIL efficacy.

Contributed by Paula Hochman

ABSTRACT: Tumor infiltrating lymphocytes (TILs) can be isolated from patient tumors, greatly expanded ex vivo, and returned to the patient for therapeutic effect. Recent clinical trials have highlighted the efficacy of TILs for a subset of patients and supported FDA approval for melanoma. How TILs evolve during the manufacturing process is still unknown and likely critical to improving the therapy for more patients. To characterize cell modification during TIL expansion, we performed single-cell RNA- and TCR-sequencing of TILs isolated from patient tumors and their paired ex vivo expanded cell products. We found large transcriptional differences between pre- and post-expansion TILs. Post-expansion TILs were predominantly exhausted and lacked nave or memory cell phenotypes, including a decreased percentage of CD39/CD69 double negative (DN) "stem-like" T cells. Co-activating receptors CD137 and CD27 decreased while CD30 increased, whereas among co-inhibitory receptors PD1 decreased while TIM3 and LAG3 showed the largest increases with expansion. Other gene families that showed large increases with ex vivo growth included cytotoxicity- and APC-associated genes. Individual clonotypes were distributed among multiple cell differentiation states, which exhibited high degrees of plasticity during expansion. Although ex vivo expanded TILs are predominantly terminally differentiated, exhausted and transcriptionally highly distinct from the initial TILs, there is also a large progenitor exhausted CD8 T cell (Tpex) population and DN numbers increase. Future work to amplify subpopulations of TILs with memory cell phenotypes, such as the DN cells, will likely further improve this therapy.

Author Info: (1) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (2) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (3) Yale University

Author Info: (1) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (2) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (3) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (4) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (5) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (6) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (7) Yale University School of Medicine New Haven, CT United States. (8) Rutgers Cancer Institute New Brunswick, NJ United States. (9) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (10) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (11) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (12) Yale University New Haven, CT United States. ROR: https://ror.org/03v76x132 (13) Yale University New Haven, Connecticut United States. ROR: https://ror.org/03v76x132

Citation: Cancer Immunol Res 2026 Feb 13 Epub02/13/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41686210

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