Journal Articles

Polymer-mRNA complexes for monocyte-trafficked, lymph node-targeted cancer vaccination Spotlight 

Qiongzhe Ren # 1, Xiaofei Zhao # 1, Lili Zhou # 2, Ruonan Ye 1, Liguo Chen 1, Keyun Ren 3, Xijun Piao 3, Yihan Zhou 4, Yiming Qi 5, Kevin C Chan 4, Li Cao 6, Liang Du 7, Peng Gao 7, Bo Ying 7, Chao Deng 1, Fenghua Meng 1, Fangfang Zhou 8, Congcong Xu 9 10 11, Zhiyuan Zhong 12 13 14

Nature biomedical engineering

To improve mRNA vaccine delivery to lymph nodes, Ren, Zhao, and Zhou et al. developed a DTC-modified, PEI-based, transferrin receptor-associating polyplex (TRAP) that enters cells by binding to TfR1, which is highly expressed on monocytes. In mice, s.c. TRAPs induced local inflammation, leading to monocyte recruitment, and effectively bound to and were taken up by TfR1high monocytes, inducing both differentiation into mo-DCs and HEV-mediated trafficking to draining lymph nodes, where mRNA translation and antigen presentation occurred. In tumor models, TRAP-mRNA vaccines elicited strong, antigen-specific, cytotoxic T cell responses, and reduced tumor progression.

Contributed by Lauren Hitchings

Qiongzhe Ren # 1, Xiaofei Zhao # 1, Lili Zhou # 2, Ruonan Ye 1, Liguo Chen 1, Keyun Ren 3, Xijun Piao 3, Yihan Zhou 4, Yiming Qi 5, Kevin C Chan 4, Li Cao 6, Liang Du 7, Peng Gao 7, Bo Ying 7, Chao Deng 1, Fenghua Meng 1, Fangfang Zhou 8, Congcong Xu 9 10 11, Zhiyuan Zhong 12 13 14

Nature biomedical engineering

To improve mRNA vaccine delivery to lymph nodes, Ren, Zhao, and Zhou et al. developed a DTC-modified, PEI-based, transferrin receptor-associating polyplex (TRAP) that enters cells by binding to TfR1, which is highly expressed on monocytes. In mice, s.c. TRAPs induced local inflammation, leading to monocyte recruitment, and effectively bound to and were taken up by TfR1high monocytes, inducing both differentiation into mo-DCs and HEV-mediated trafficking to draining lymph nodes, where mRNA translation and antigen presentation occurred. In tumor models, TRAP-mRNA vaccines elicited strong, antigen-specific, cytotoxic T cell responses, and reduced tumor progression.

Contributed by Lauren Hitchings

ABSTRACT: Lymph nodes are the primary sites where adaptive immunity is initiated, yet most messenger RNA cancer vaccines reach them inefficiently and instead accumulate in organs such as the liver, limiting therapeutic potency and increasing systemic toxicity. Here we developed a transferrin receptor-associating polyplex formed by electrostatic complexation of mRNA with low-molecular-weight polyethylenimine that had been chemically modified with cyclic disulfide monomers to enhance nucleic acid binding stability, enable thiol-based transferrin receptor engagement and reduce off-target liver uptake. After subcutaneous administration, these polyplexes activated innate immunity, rapidly recruited monocytes with high transferrin receptor expression and bound these cells through cyclic disulfide-mediated interactions. Monocytes then trafficked the vaccine to draining lymph nodes, where mRNA translation and antigen presentation occurred. Delivery of ovalbumin and interleukin 12 mRNA elicited strong antigen-specific cytotoxic T cell responses and inhibited melanoma progression and metastatic disease. Studies using Survivin and human papillomavirus antigens in distinct tumour models demonstrated broad applicability. This monocyte-driven lymph node-targeting strategy enables potent and selective delivery of mRNA cancer vaccines.

Author Info: 1Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, P. R. China. 2Institutes of Biology and Medical Scien

Author Info: 1Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, P. R. China. 2Institutes of Biology and Medical Science, Soochow University, Suzhou, P. R. China. 3Catug Biotechnology Co. Ltd, Suzhou, P. R. China. 4Department of Biosciences and Bioinformatics, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, P. R. China. 5School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China. 6College of Pharmaceutical Sciences, Soochow University, Suzhou, P. R. China. 7Suzhou Abogen Biosciences Co. Ltd, Suzhou, P. R. China. 8Institutes of Biology and Medical Science, Soochow University, Suzhou, P. R. China. zhoufangfang@suda.edu.cn. 9Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, P. R. China. xucc@suda.edu.cn. 10College of Pharmaceutical Sciences, Soochow University, Suzhou, P. R. China. xucc@suda.edu.cn. 11International College of Pharmaceutical Innovation, Soochow University, Suzhou, P. R. China. xucc@suda.edu.cn. 12Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, P. R. China. zyzhong@suda.edu.cn. 13College of Pharmaceutical Sciences, Soochow University, Suzhou, P. R. China. zyzhong@suda.edu.cn. 14International College of Pharmaceutical Innovation, Soochow University, Suzhou, P. R. China. zyzhong@suda.edu.cn. #Contributed equally.

Citation: Nat Biomed Eng 2026 May 5 Epub05/05/2026

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42086923

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    Ferroptosis-armed dendritic cell vaccines for glioma immunotherapy Spotlight 

    Mariia Saviuk 1 2, Victoria D Turubanova 1 3, Sara De Brée 1 2, Sandra Van Lint 2 4, Teresa Mendes Maia 5 6 7, Simon Devos 5 6 7, Iuliia Efimova 1 2, Julie Braet 2 4, Lore Van Oudenhove 8, Gitta Boons 8, Faye Naessens 1 2, Robin Demuynck 1 2, Ellen Saeys 1 2, Christian Vanhove 9, Lukas Bunse 10 11, Peter M van Endert 12 13, Robrecht Raedt 14, Maria V Vedunova 15, Olga Krysko 1, Roosmarijn E Vandenbroucke 16 17, Karim Vermaelen 2 4, Tatiana A Mishchenko 15, Elena Catanzaro # 18 19, Dmitri V Krysko # 1 2

    Nature communications

    A prophylactic DC vaccine loaded with ferroptotic (iron-dependent cell death) glioma cell line lysates protected against glioma growth in mice, superior to immunogenic cell death (ICD) or freeze/thaw (non-ICD) lysates. The vaccine also mediated therapeutic efficacy, induced antigen-specific CTL responses in SLOs, and increased i.t. CTLs (particularly CD39+ effector-memory cells) compared to controls. Ferroptosis induced ICD markers on glioma cells, and blocking calreticulin or ATP, but not HMGB1, abrogated vaccine efficacy. Ferroptotic lysates activated DCs and displayed a unique proteomic profile, potentially presenting novel TAAs.

    Contributed by Alex Najibi

    Mariia Saviuk 1 2, Victoria D Turubanova 1 3, Sara De Brée 1 2, Sandra Van Lint 2 4, Teresa Mendes Maia 5 6 7, Simon Devos 5 6 7, Iuliia Efimova 1 2, Julie Braet 2 4, Lore Van Oudenhove 8, Gitta Boons 8, Faye Naessens 1 2, Robin Demuynck 1 2, Ellen Saeys 1 2, Christian Vanhove 9, Lukas Bunse 10 11, Peter M van Endert 12 13, Robrecht Raedt 14, Maria V Vedunova 15, Olga Krysko 1, Roosmarijn E Vandenbroucke 16 17, Karim Vermaelen 2 4, Tatiana A Mishchenko 15, Elena Catanzaro # 18 19, Dmitri V Krysko # 1 2

    Nature communications

    A prophylactic DC vaccine loaded with ferroptotic (iron-dependent cell death) glioma cell line lysates protected against glioma growth in mice, superior to immunogenic cell death (ICD) or freeze/thaw (non-ICD) lysates. The vaccine also mediated therapeutic efficacy, induced antigen-specific CTL responses in SLOs, and increased i.t. CTLs (particularly CD39+ effector-memory cells) compared to controls. Ferroptosis induced ICD markers on glioma cells, and blocking calreticulin or ATP, but not HMGB1, abrogated vaccine efficacy. Ferroptotic lysates activated DCs and displayed a unique proteomic profile, potentially presenting novel TAAs.

    Contributed by Alex Najibi

    ABSTRACT: The type of cell death has proven to play a crucial role in cancer immunotherapy efficacy. Immunogenic cell death (ICD) enhances tumor adjuvanticity and antigenicity by releasing danger signals and altering the immune peptidome. The immunogenicity of ferroptosis, an iron-dependent form of cell death, remains uncertain. Here, we show that dendritic cell (DC) vaccines loaded with ferroptotic lysates protect mice against glioma growth, inducing IFN-_ production, and promoting robust CD8_ T cell infiltration, activation, and effector memory formation in the tumor microenvironment. The intrinsic immunogenicity of ferroptosis was independent of the glioma type and the ferroptosis inducer. Instead, it critically required the presence of the damage-associated molecular patterns calreticulin and ATP, rather than involving HMGB1-TLR4 signaling. However, supplementing these DAMPs into DC vaccines loaded with non-ICD lysates did not restore efficacy to the level of the ferroptosis-based DC vaccine, suggesting a more complex mechanism beyond a purely DAMP-mediated effect. These findings demonstrate that ferroptosis-loaded DC vaccines elicit a potent, tumor-specific immune response, capable of eradicating intracranial gliomas in mice, which highlights their potential in cancer immunotherapy.

    Author Info: 1Cell Death Investigation and Therapy (CDIT) Laboratory, Anatomy and Embryology Unit, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent Unive

    Author Info: 1Cell Death Investigation and Therapy (CDIT) Laboratory, Anatomy and Embryology Unit, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. 2Cancer Research Institute Ghent, Ghent, Belgium. 3Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny, Russia. 4Thoracic Tumor Immunology Laboratory (TTIL), Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Science, Ghent University, Ghent, Belgium. 5VIB Proteomics Core, VIB, Ghent, Belgium. 6VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium. 7Department of Biomolecular Medicine, Ghent University, Ghent, Belgium. 8myNEO Therapeutics, Ghent, Belgium. 9IBiTech-MEDISIP-Infinity Laboratory, Department of Electronics and Information Systems, Faculty of Engineering and Architecture, Ghent University, Ghent, Belgium. 10Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 11Neurology Clinic, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany. 12Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, Paris, France. 13Service Immunologie Biologique, AP-HP, Hôpital Universitaire Necker-Enfants Malades, Paris, France. 144Brain, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. 15Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny, Russia. 16VIB Center for Inflammation Research, Ghent, Belgium. 17Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium. 18Cell Death Investigation and Therapy (CDIT) Laboratory, Anatomy and Embryology Unit, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. elena.catanzaro@ugent.be. 19Cancer Research Institute Ghent, Ghent, Belgium. elena.catanzaro@ugent.be. #Contributed equally.

    Citation: Nat Commun 2026 May 7 Epub05/07/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42098128

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      Intermetallic nanoassemblies potentiate systemic STING activation Spotlight 

      Xingwu Zhou # 1 2, Xiang Ling # 1 2, Xiaoqi Sun 1 2, Ziye Wan 1 2, Tobias Dwyer 3, Timothy C Moore 3, Quguang Li 1 2, Hannah E Dobson 1 2, Qi Wu 1 2, Xiangbo Kong 4, Fang Xie 1 2, Xinran An 1 2, Jingyao Gan 1 2, Kaikai Wang 1 2, Young Seok Cho 1 2, Wang Gong 5, Katherine Dong 1 2, Jie Zhang 1 2, Mariko Takahashi 1 2, Cheng Xu 1 2, Swetha Kodamasimham 1 2, Jie Xu 4, Vilma Yuzbasiyan-Gurkan 6 7, Steven B Chinn 8, Anna Schwendeman 1 2, Sharon C Glotzer 2 3, Yu Leo Lei 5, James J Moon 1 2 3 9 10

      Science

      Zhou, and Ling et al. engineered CRYSTAL, a crystal-like STING-activating nanoassembly, to stabilize a STING agonist and enhance STING signaling at lower doses. Intravenous CRYSTAL activated myeloid cells, remodeled immunosuppressive tumor microenvironments, and primed host STING-dependent CD8+ T cell responses, driving durable tumor regression in advanced murine and rabbit models. Across mice, dogs, and non-human primates, CRYSTAL induced potent, but transient interferon responses, without cytokine release syndrome. Ex vivo treatment of human head and neck cancer biopsies triggered strong interferon signaling.

      Contributed by Shishir Pant

      Xingwu Zhou # 1 2, Xiang Ling # 1 2, Xiaoqi Sun 1 2, Ziye Wan 1 2, Tobias Dwyer 3, Timothy C Moore 3, Quguang Li 1 2, Hannah E Dobson 1 2, Qi Wu 1 2, Xiangbo Kong 4, Fang Xie 1 2, Xinran An 1 2, Jingyao Gan 1 2, Kaikai Wang 1 2, Young Seok Cho 1 2, Wang Gong 5, Katherine Dong 1 2, Jie Zhang 1 2, Mariko Takahashi 1 2, Cheng Xu 1 2, Swetha Kodamasimham 1 2, Jie Xu 4, Vilma Yuzbasiyan-Gurkan 6 7, Steven B Chinn 8, Anna Schwendeman 1 2, Sharon C Glotzer 2 3, Yu Leo Lei 5, James J Moon 1 2 3 9 10

      Science

      Zhou, and Ling et al. engineered CRYSTAL, a crystal-like STING-activating nanoassembly, to stabilize a STING agonist and enhance STING signaling at lower doses. Intravenous CRYSTAL activated myeloid cells, remodeled immunosuppressive tumor microenvironments, and primed host STING-dependent CD8+ T cell responses, driving durable tumor regression in advanced murine and rabbit models. Across mice, dogs, and non-human primates, CRYSTAL induced potent, but transient interferon responses, without cytokine release syndrome. Ex vivo treatment of human head and neck cancer biopsies triggered strong interferon signaling.

      Contributed by Shishir Pant

      ABSTRACT: Natural systems use metal ions to form ordered structures that regulate biological processes, inspiring the rational design of nanotherapeutics. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway drives antitumor immunity but has been difficult to activate systemically owing to poor pharmacology and toxicity. Here, we report CRYSTAL, a structurally ordered intermetallic nanoparticle for potent systemic STING activation. CRYSTAL self-assembles from manganese ions intercalated with cyclic dinucleotides, enabling precise structural control. At an ultralow intravenous dose (0.003 milligrams per kilogram), CRYSTAL activated STING in mice, dogs, and nonhuman primates without cytokine release syndrome. CRYSTAL induced robust tumor regression in advanced murine and rabbit models, remodeled immunosuppressive environments, and promoted host STING-dependent CD8(+) T cell priming. CRYSTAL activated interferon responses in human head and neck squamous cell carcinoma biopsies, underscoring its translational potential for cancer immunotherapy.

      Author Info: 1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. 2Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. 3Department of Chemical En

      Author Info: 1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. 2Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. 3Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. 4Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, MI, USA. 5Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6Department of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, USA. 7Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA. 8Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA. 9Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. 10Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. #Contributed equally.

      Citation: Science 2026 May 7 392:eadx1893 Epub05/07/2026

      Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42096576

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        Safety and efficacy of intratumoural anti-CTLA4 with intravenous anti-PD1 Featured  

        (1) Tselikas L (2) Susini S (3) Texier M (4) Yurchenko A (5) Routier E (6) Amini-Adle M (7) Tihic E (8) Mouraud S (9) Danlos FX (10) Ammari S (11) Raoult T (12) Roy S (13) Bredel D (14) Farhane S (15) Cassard L (16) Molinaro I (17) Eggermont A (18) Soria JC (19) Zitvogel L (20) Massard C (21) Paci A (22) de Baere T (23) Scoazec JY (24) Chaput N (25) Nikolaev S (26) Meyer N (27) LebbŽ C (28) Dalle S (29) Robert C (30) Marabelle A

        Nature

        Tselikas and Susini et al. reported the results of the phase 1b NIVIPIT trial, in which 61 patients with untreated metastatic melanoma were treated with intravenous (i.v.) nivolumab (anti-PD-1) in combination with either i.v. or intratumoral (i.t.) ipilimumab (anti-CTLA-4). Patients who received i.t. anti-CTLA-4 had antitumor responses in both injected and uninjected lesions, and had fewer grade 3 or 4 treatment-related adverse events. The presence of Tregs and M2-like macrophages at baseline, high FcγR expression, and a decrease in activated Tregs on treatment were associated with durable clinical benefit, regardless of the anti-CTLA-4 administration route.

        (1) Tselikas L (2) Susini S (3) Texier M (4) Yurchenko A (5) Routier E (6) Amini-Adle M (7) Tihic E (8) Mouraud S (9) Danlos FX (10) Ammari S (11) Raoult T (12) Roy S (13) Bredel D (14) Farhane S (15) Cassard L (16) Molinaro I (17) Eggermont A (18) Soria JC (19) Zitvogel L (20) Massard C (21) Paci A (22) de Baere T (23) Scoazec JY (24) Chaput N (25) Nikolaev S (26) Meyer N (27) LebbŽ C (28) Dalle S (29) Robert C (30) Marabelle A

        Nature

        Tselikas and Susini et al. reported the results of the phase 1b NIVIPIT trial, in which 61 patients with untreated metastatic melanoma were treated with intravenous (i.v.) nivolumab (anti-PD-1) in combination with either i.v. or intratumoral (i.t.) ipilimumab (anti-CTLA-4). Patients who received i.t. anti-CTLA-4 had antitumor responses in both injected and uninjected lesions, and had fewer grade 3 or 4 treatment-related adverse events. The presence of Tregs and M2-like macrophages at baseline, high FcγR expression, and a decrease in activated Tregs on treatment were associated with durable clinical benefit, regardless of the anti-CTLA-4 administration route.

        ABSTRACT: Intravenous administration of anti-CTLA4 with anti-PD1 provides durable tumour responses but causes severe treatment-related adverse events in patients with cancer(1). Intratumoural administration at lower doses but high local concentrations could enhance antitumour efficacy while minimizing systemic exposure and toxicity. Here we report the randomized multicentre phase 1b NIVIPIT trial (ClinicalTrials.gov: NCT02857569 ), which enrolled 61 patients with untreated metastatic melanoma, randomly assigned 2:1 to receive intravenous nivolumab (anti-PD1; 1_mg_kg(-1)) combined with either intratumoural ipilimumab (anti-CTLA4; 0.3_mg_kg(-1)) or intravenous ipilimumab (3_mg_kg(-1)). The primary end-point was met with significantly lower incidence of grade 3 or 4 treatment-related adverse events at 6 months in the intratumoural versus intravenous arm (22.6% versus 57.1%), equivalent to anti-PD1 monotherapy. RECIST (response evaluation criteria in solid tumours) best objective response rate reached 65.7% for anti-CTLA4 injected lesions and 50% for uninjected lesions, confirming the relationship between intratumoural exposure to anti-CTLA4 and efficacy. Baseline tumour immune profiling revealed that protumoural activated regulatory T (T(reg)) cells and M2 macrophages predict durable clinical benefit, regardless of the anti-CTLA4 administration route. A decrease in activated intratumoural T(reg) cells occurred only in patients who showed durable clinical benefit, who also presented high intratumoural Fc_ receptor (Fc_R) expression. Our results provide a rationale for intratumoural anti-CTLA4 strategies in oligometastatic and early-stage cancers and indicate that high intratumoural activated T(reg) cell and Fc_R(+) M2 macrophage numbers are prerequisites for efficacy of combined anti-CTLA4 and anti-PD1.

        Author Info: (1) INSERM CIC 1428, BIOTHERIS, Villejuif, France. INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. Gustave Roussy, Radiologie I

        Author Info: (1) INSERM CIC 1428, BIOTHERIS, Villejuif, France. INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. Gustave Roussy, Radiologie Interventionnelle, DŽpartement d'AnesthŽsie Chirurgie et Interventionnel (DACI), Villejuif, France. UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. (2) INSERM CIC 1428, BIOTHERIS, Villejuif, France. INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. (3) Gustave Roussy, Service de Biostatistiques et d'EpidŽmiologie (SBE), UniversitŽ Paris Saclay, Villejuif, France. INSERM U1018, ONCOSTAT, Equipe LabellisŽe Ligue contre le Cancer, Villejuif, France. (4) INSERM U981, Gustave Roussy, Villejuif, France. (5) Gustave Roussy, Dermatologie, DŽpartement de MŽdecine Oncologique, Villejuif, France. (6) Hospices Civils de Lyon, DŽpartement de Dermatologie, Lyon, France. (7) INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. (8) INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. (9) INSERM CIC 1428, BIOTHERIS, Villejuif, France. INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. (10) Gustave Roussy, DŽpartement d'Imagerie MŽdicale, Villejuif, France. (11) Gustave Roussy, Service de Promotion d'Etudes Cliniques, DRC, Villejuif, France. (12) INSERM U981, Gustave Roussy, Villejuif, France. Gustave Roussy, Dermatologie, DŽpartement de MŽdecine Oncologique, Villejuif, France. (13) INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. (14) INSERM CIC 1428, BIOTHERIS, Villejuif, France. (15) UniversitŽ Paris-Saclay, Gustave Roussy, INSERM, Laboratoire d'Immunomonitoring en Oncologie US23, BiothŽrapies Innovantes U1363, Villejuif, F-94805, France. (16) Gustave Roussy, DŽpartement de Biologie et Pathologie MŽdicale, Villejuif, France. (17) UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. INSERM U981, Gustave Roussy, Villejuif, France. Gustave Roussy, Dermatologie, DŽpartement de MŽdecine Oncologique, Villejuif, France. (18) UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. Gustave Roussy, DŽpartement d'Innovation ThŽrapeutique et des Essais PrŽcoces, Villejuif, France. (19) UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. INSERM U1015, Immunologie des tumeurs et immunothŽrapie contre le cancer, Villejuif, France. (20) UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. Gustave Roussy, DŽpartement d'Innovation ThŽrapeutique et des Essais PrŽcoces, Villejuif, France. (21) UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. Gustave Roussy, Service de Pharmacologie, DŽpartement de Biologie et Pathologie mŽdicales, Villejuif, France. (22) INSERM CIC 1428, BIOTHERIS, Villejuif, France. Gustave Roussy, Radiologie Interventionnelle, DŽpartement d'AnesthŽsie Chirurgie et Interventionnel (DACI), Villejuif, France. UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. (23) UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. Gustave Roussy, DŽpartement de Biologie et Pathologie MŽdicale, Villejuif, France. (24) UniversitŽ Paris-Saclay, Gustave Roussy, INSERM, Laboratoire d'Immunomonitoring en Oncologie US23, BiothŽrapies Innovantes U1363, Villejuif, F-94805, France. (25) INSERM U981, Gustave Roussy, Villejuif, France. (26) CHU de Toulouse, Service d'Oncodermatologie, IUCT-O, Toulouse, France. INSERM UMR 1037, Cancer Research Center of Toulouse (CRCT), Toulouse, France. UniversitŽ Toulouse III - Paul Sabatier, DŽpartement de Dermatologie, Toulouse, France. (27) UniversitŽ Paris CitŽ, AP-HP Dermato-oncologie et CIC, Institut du Cancer APHP nord, Paris, France. INSERM U1342-Equipe 1-CNRS EMR8000, H™pital Saint Louis, Paris, France. (28) Hospices Civils de Lyon, DŽpartement de Dermatologie, Lyon, France. INSERM U1052-CNRS UMR5286, PlasticitŽ Tumorale dans le MŽlanome, Centre de Recherche en CancŽrologie de Lyon, Centre LŽon BŽrard, Lyon, France. UniversitŽ Claude Bernard Lyon 1, Lyon, France. (29) UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. INSERM U981, Gustave Roussy, Villejuif, France. Gustave Roussy, Dermatologie, DŽpartement de MŽdecine Oncologique, Villejuif, France. (30) INSERM CIC 1428, BIOTHERIS, Villejuif, France. aurelien.marabelle@gustaveroussy.fr. INSERM U1015, Laboratoire de Recherche Translationnelle en ImmunothŽrapie (LRTI), Villejuif, France. aurelien.marabelle@gustaveroussy.fr. UniversitŽ Paris Saclay, Faculty of Medicine, Villejuif, France. aurelien.marabelle@gustaveroussy.fr. Gustave Roussy, DŽpartement d'Innovation ThŽrapeutique et des Essais PrŽcoces, Villejuif, France. aurelien.marabelle@gustaveroussy.fr.

        Citation: Nature 2026 Apr 29 Epub04/29/2026

        Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42056527

        Tags:

        The circadian gene Dec2 promotes pancreatic cancer progression and dormancy through immune evasion Spotlight 

        (1) Wang L (2) Harris CR (3) Dudgeon C (4) Prela O (5) Cazares de Menezes J (6) Shih CH (7) Davidson C (8) Casabianca A (9) De S (10) Narrow W (11) Becker J (12) Grandgenett PM (13) Hollingsworth MA (14) Grem JL (15) Kim M (16) Hong Y (17) Gerber S (18) Vertino PM (19) Gao C (20) Klamer Z (21) Repesh A (22) Hao Y (23) Ryan AT (24) Breitenbach M (25) Bianchi A (26) Datta J (27) Altman BJ (28) Haab B (29) Carpizo DR

        Developmental cell

        Wang, Harris, and Dudgeon et al. identified the circadian rhythm gene Dec2 as a tumor-intrinsic regulator of dormancy and immune evasion in pancreatic cancer models. Dormant PDAC cells and occult disseminated tumor cells expressed high levels of Dec2, which repressed multiple components of the MHC-I antigen presentation pathway and reduced T cell-mediated cytotoxicity. Tumor surface MHC-I levels oscillated in antiphase to Dec2. Dec2 deletion restored antigen presentation, repolarized the PDAC TME from immune-cold to inflamed, and improved survival in immunocompetent (Ink4a.1 and 6419c5 models), but not immunodeficient mice.

        Contributed by Shishir Pant

        (1) Wang L (2) Harris CR (3) Dudgeon C (4) Prela O (5) Cazares de Menezes J (6) Shih CH (7) Davidson C (8) Casabianca A (9) De S (10) Narrow W (11) Becker J (12) Grandgenett PM (13) Hollingsworth MA (14) Grem JL (15) Kim M (16) Hong Y (17) Gerber S (18) Vertino PM (19) Gao C (20) Klamer Z (21) Repesh A (22) Hao Y (23) Ryan AT (24) Breitenbach M (25) Bianchi A (26) Datta J (27) Altman BJ (28) Haab B (29) Carpizo DR

        Developmental cell

        Wang, Harris, and Dudgeon et al. identified the circadian rhythm gene Dec2 as a tumor-intrinsic regulator of dormancy and immune evasion in pancreatic cancer models. Dormant PDAC cells and occult disseminated tumor cells expressed high levels of Dec2, which repressed multiple components of the MHC-I antigen presentation pathway and reduced T cell-mediated cytotoxicity. Tumor surface MHC-I levels oscillated in antiphase to Dec2. Dec2 deletion restored antigen presentation, repolarized the PDAC TME from immune-cold to inflamed, and improved survival in immunocompetent (Ink4a.1 and 6419c5 models), but not immunodeficient mice.

        Contributed by Shishir Pant

        ABSTRACT: The mechanisms that regulate immune evasion by pancreatic ductal adenocarcinomas (PDACs) remain poorly understood. Using a mouse model of resectable PDAC, we identified an unknown role of the circadian rhythm gene Differentially Expressed in Chondrocytes 2 (Dec2) in regulating tumor progression and dormancy. Deletion of Dec2 from tumor cells substantially increased mouse survival after resection due to an immune-mediated mechanism, as the survival benefit was abrogated under immunodeficient conditions. Dec2 promotes immune evasion by repressing major histocompatibility complex class I (MHC-I)-dependent antigen presentation and by repolarizing the tumor microenvironment from immunologically cold (low T cell infiltration) to hot (elevated T cell infiltration). Dec2 is also a regulator of circadian rhythms, and we found that genes involved in MHC-I antigen presentation and MHC-I surface localization oscillated in a circadian manner, which was lost upon deletion of Dec2 in vitro. We conclude that Dec2 promotes primary PDAC progression and likely metastatic dormancy through immune evasion.

        Author Info: (1) Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (2) Department of Surgery, Division of Surgical O

        Author Info: (1) Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (2) Department of Surgery, Division of Surgical Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (3) Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. (4) Department of Surgery, Division of Surgical Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (5) Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (6) Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (7) Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (8) Department of Surgery, Division of Surgical Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (9) Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. (10) Department of Surgery, Division of Surgical Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. (11) Dewitt Daughtry Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA. (12) Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. (13) Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. (14) Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. (15) Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (16) Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI, USA. (17) Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI, USA. (18) Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA; Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (19) Center for Advanced Research Technologies, University of Rochester Medical Center, Rochester, NY, USA. (20) Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI, USA. (21) Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI, USA. (22) Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (23) Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (24) Department of Surgery, Division of Surgical Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (25) Dewitt Daughtry Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA. (26) Dewitt Daughtry Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA. (27) Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA; Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. (28) Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI, USA. (29) Department of Surgery, Division of Surgical Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA; Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: darren_carpizo@urmc.rochester.edu.

        Citation: Dev Cell 2026 Apr 28 Epub04/28/2026

        Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42055006

        Tags:

        Time-of-day of first checkpoint inhibitor dose influences clinical outcomes and immune responses in hepatocellular carcinoma Spotlight 

        (1) Li HL (2) Charmsaz S (3) Reisman BJ (4) Hayek F (5) Brancati M (6) Leatherman JM (7) Pazzi C (8) Lee RP (9) Zhao X (10) Christenson E (11) Arif W (12) Hernandez J (13) Ellis C (14) Gross NE (15) Thoburn C (16) Chandler GS (17) Mohindra R (18) Bansal S (19) Tang L (20) Guha A (21) Dang CV (22) Zaidi N (23) Jaffee EM (24) Laheru D (25) Zabransky DJ (26) Barretti M (27) Ho WJ (28) Yarchoan M (29) Nakazawa M

        Journal for immunotherapy of cancer | Free PMC Article

        Among a retrospective cohort of 84 HCC patients treated with ICB, those who received their first ICB dose in the morning (prior to 12 noon) had increased PFS (and a trend in OS) compared to those receiving a first dose in the afternoon. The timing of subsequent doses did not have a similar stratifying effect, and morning dosing did not raise the rate of irAEs. Comparing baseline and early on-treatment blood samples, Li et al. found that patients first receiving ICB in the morning had diminished induction of certain cytokines (IL-6, IL-1B, VEGF-A, and IL-21) and a greater expansion of cytotoxic CD8+ Tcm cells, compared to those receiving an afternoon dose.

        Contributed by Alex Najibi

        (1) Li HL (2) Charmsaz S (3) Reisman BJ (4) Hayek F (5) Brancati M (6) Leatherman JM (7) Pazzi C (8) Lee RP (9) Zhao X (10) Christenson E (11) Arif W (12) Hernandez J (13) Ellis C (14) Gross NE (15) Thoburn C (16) Chandler GS (17) Mohindra R (18) Bansal S (19) Tang L (20) Guha A (21) Dang CV (22) Zaidi N (23) Jaffee EM (24) Laheru D (25) Zabransky DJ (26) Barretti M (27) Ho WJ (28) Yarchoan M (29) Nakazawa M

        Journal for immunotherapy of cancer | Free PMC Article

        Among a retrospective cohort of 84 HCC patients treated with ICB, those who received their first ICB dose in the morning (prior to 12 noon) had increased PFS (and a trend in OS) compared to those receiving a first dose in the afternoon. The timing of subsequent doses did not have a similar stratifying effect, and morning dosing did not raise the rate of irAEs. Comparing baseline and early on-treatment blood samples, Li et al. found that patients first receiving ICB in the morning had diminished induction of certain cytokines (IL-6, IL-1B, VEGF-A, and IL-21) and a greater expansion of cytotoxic CD8+ Tcm cells, compared to those receiving an afternoon dose.

        Contributed by Alex Najibi

        BACKGROUND: Although immune checkpoint inhibitors (ICIs) have long half-lives, preclinical and retrospective clinical studies across multiple tumor types suggest that the time-of-day of ICI infusion may influence therapeutic efficacy by aligning initial drug exposure with circadian peaks in T-cell responsiveness. The immunological basis of this phenomenon and its clinical relevance in hepatocellular carcinoma (HCC) remains unknown. METHODS: We followed patients with advanced HCC receiving ICI therapy at Johns Hopkins from 2021 to 2025, classifying them into a morning (first treatment before 12:00 hours) or afternoon (first treatment after 12:00 hours) group. We assessed clinical outcomes and compared immunological responses from baseline to early-on-treatment by profiling peripheral blood mononuclear cells using cytometry by time-of-flight and plasma cytokines using a 39-plex Luminex assay. RESULTS: Our cohort included 84 patients, 39 of whom received their first infusion in the morning. There were no statistically significant differences in baseline demographic or clinical characteristics between patients initiating therapy in the morning versus afternoon. The morning group had superior progression-free survival (multivariable HR 0.50, 95% CI 0.30 to 0.84, p<0.01) and higher odds of treatment response (multivariable OR 3.26, 95% CI 1.08 to 10.90, p<0.05), with no significant increase in immune-related adverse events. The timing of subsequent infusions after the first dose had no impact on outcomes. Immunological responses diverged after the initial dose, with morning-treated patients showing reduced interleukin (IL)-6 levels (p<0.01) and greater expansion of cytotoxic central memory CD8+ T_cells (p=0.01) as well as cytotoxic effector and effector memory CD8+ T_cells (p=0.06). CONCLUSIONS: Morning first-dose infusion of ICIs in HCC was associated with improved clinical outcomes and distinct immune responses, including reduced IL-6 signaling and expansion of cytotoxic central memory CD8+ T cells. These findings suggest that the timing of the initial infusion can imprint an immunological program that shapes subsequent antitumor immunity, providing a mechanistic rationale for strategically scheduling ICI administration.

        Author Info: (1) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. (2) Sidney

        Author Info: (1) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. (2) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (3) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (4) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (5) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (6) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (7) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (8) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. (9) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (10) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (11) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (12) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (13) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (14) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (15) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (16) F Hoffmann-La Roche Ltd, Basel, Switzerland. (17) F Hoffmann-La Roche Ltd, Basel, Switzerland. Genentech Inc, South San Francisco, California, USA. (18) Genentech Inc, South San Francisco, California, USA. (19) Genentech Inc, South San Francisco, California, USA. (20) Genentech Inc, South San Francisco, California, USA. (21) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. Ludwig Institute for Cancer Research, Baltimore, Maryland, USA. (22) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (23) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (24) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (25) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (26) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (27) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. (28) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA mark.yarchoan@jhmi.edu mnakaza2@jhmi.edu. (29) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA mark.yarchoan@jhmi.edu mnakaza2@jhmi.edu.

        Citation: J Immunother Cancer 2026 Apr 21 14: Epub04/21/2026

        Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42014205

        Tags:

        Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity Spotlight 

        (1) Hu M (2) Liu DA (3) Wortzel I (4) Collier P (5) Nelson TM (6) Foox J (7) Zhong G (8) Tobias G (9) Asao T (10) Bojmar L (11) Kenific CM (12) Wang G (13) Caielli S (14) Wan Z (15) Qureshy S (16) Reed M (17) Piszczatowski R (18) Ravisankar P (19) Brown JA (20) Xiong S (21) Wang H (22) Lauritzen P (23) Aylon Y (24) Molina H (25) Jarnagin WR (26) Oren M (27) Stanger BZ (28) Bui J (29) Bergers G (30) No‘l A (31) Grandgenett PM (32) Hollingsworth MA (33) Tuveson D (34) Boudreau N (35) Bromberg J (36) Kelsen D (37) Jones DR (38) Santambrogio L (39) Zeng MY (40) Pascual V (41) Kim HS (42) Mason CE (43) Zhang H (44) Matei IR (45) Lyden D

        Cancer cell

        Hu and Liu et al. found that activated T cells secreted abundant extracellular vesicular DNA (AT-EVDNA) that was mainly from newly made genomic DNA and was rich in immune-related genes. Upon uptake of EVs by tumor cells or dendritic cells, granzyme B encapsulated in the EVs disrupted the nuclear envelope and facilitated entry of EVDNA into the nucleus, where transient expression of the EVDNA increased antigen processing and presentation machinery and cytokine production, enhancing immunogenicity. In mouse models, AT-EVs overcame immune evasion and boosted immune checkpoint blockade, supporting their potential use as an acellular immunotherapy.

        Contributed by Lauren Hitchings

        (1) Hu M (2) Liu DA (3) Wortzel I (4) Collier P (5) Nelson TM (6) Foox J (7) Zhong G (8) Tobias G (9) Asao T (10) Bojmar L (11) Kenific CM (12) Wang G (13) Caielli S (14) Wan Z (15) Qureshy S (16) Reed M (17) Piszczatowski R (18) Ravisankar P (19) Brown JA (20) Xiong S (21) Wang H (22) Lauritzen P (23) Aylon Y (24) Molina H (25) Jarnagin WR (26) Oren M (27) Stanger BZ (28) Bui J (29) Bergers G (30) No‘l A (31) Grandgenett PM (32) Hollingsworth MA (33) Tuveson D (34) Boudreau N (35) Bromberg J (36) Kelsen D (37) Jones DR (38) Santambrogio L (39) Zeng MY (40) Pascual V (41) Kim HS (42) Mason CE (43) Zhang H (44) Matei IR (45) Lyden D

        Cancer cell

        Hu and Liu et al. found that activated T cells secreted abundant extracellular vesicular DNA (AT-EVDNA) that was mainly from newly made genomic DNA and was rich in immune-related genes. Upon uptake of EVs by tumor cells or dendritic cells, granzyme B encapsulated in the EVs disrupted the nuclear envelope and facilitated entry of EVDNA into the nucleus, where transient expression of the EVDNA increased antigen processing and presentation machinery and cytokine production, enhancing immunogenicity. In mouse models, AT-EVs overcame immune evasion and boosted immune checkpoint blockade, supporting their potential use as an acellular immunotherapy.

        Contributed by Lauren Hitchings

        ABSTRACT: Antigen processing and presentation (APP) is essential for adaptive immunosurveillance. We uncover a mechanism whereby activated T cell-derived extracellular vesicles (AT(EVs)) drive a positive feedback loop that enhances antigen presentation and immune responses in normal physiology and cancer. AT(EV)-induced immunogenicity relies on extracellular vesicular double-stranded DNA (EV(DNA)), which is notably abundant and primarily composed of genomic DNA enriched in immune-related genes, including those encoding APP machinery. Mechanistically, granzyme B (Gzmb) packaged by AT(EVs) disrupts the nuclear envelope of recipient cells, facilitating intranuclear transfer and subsequent transient expression of EV(DNA) encoding APP genes. DNase treatment removes most AT-EV(DNA), abrogating APP upregulation and thus T cell activation and recruitment to tumors. Notably, AT(EVs) hold promise as an acellular immunotherapy, restoring APP and synergizing with checkpoint blockade in immunotherapy-refractory tumors. Collectively, our findings uncover a mechanism of transient, non-viral gene delivery by AT(EVs) that boosts APP and anti-tumor immunity while limiting autoimmunity.

        Author Info: (1) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center

        Author Info: (1) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA. (2) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (3) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (4) Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA. (5) Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA. (6) Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA. (7) Department of Systems Biology, Columbia University, New York, NY, USA. (8) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (9) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Respiratory Medicine, Juntendo University, Tokyo, Japan. (10) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Department of Biomedical and Clinical Sciences, Linkšping University, Linkšping, Sweden. (11) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (12) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (13) Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. (14) Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. (15) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (16) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (17) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (18) Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. (19) Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. (20) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (21) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (22) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (23) Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. (24) Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA. (25) Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (26) Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. (27) Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (28) Department of Pathology, University of California, San Diego, La Jolla, CA, USA. (29) Laboratory of Tumor Microenvironment and Therapeutic Resistance, KU Leuven, Leuven, Belgium. (30) Laboratory of Biology of Tumor and Development, UniversitŽ de Lige, Lige, Belgium. (31) Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. (32) Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. (33) Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724, USA. (34) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (35) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (36) Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (37) Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (38) Department of Radiation Oncology, Weill Cornell School of Medicine, New York, NY, USA. (39) Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. (40) Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. (41) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. (42) Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA. (43) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. Electronic address: haz2005@med.cornell.edu. (44) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. Electronic address: irm2224@med.cornell.edu. (45) Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. Electronic address: dcl2001@med.cornell.edu.

        Citation: Cancer Cell 2026 Apr 30 Epub04/30/2026

        Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42066762

        Tags:

        Intratumoral Treg cell ablation elicits NK cell-mediated control of CD8 T cell-resistant tumors

        Featured  

        (1) Zhang C (2) Chien C (3) Jurgaityt_ E (4) Sakiyama K (5) Bockman A (6) Jo Y (7) Lee S (8) Silveria S (9) Andrews E (10) Mende A (11) Zhang L (12) Garcia KC (13) Wagner A (14) DuPage M (15) Raulet D

        Science immunology

        Zhang et al. found that intratumoral depletion of Tregs elicited potent antitumor NK cell responses that controlled MHC-I-deficient and even MHC-I-proficient cancers expressing sufficient NKG2D ligands. This effect was dependent on cDC2-mediated activation of CD4+ T cells and their subsequent production of IL-2, which directly enhanced NK cell activation and cytotoxic potential. Antibody-mediated depletion of intratumoral Tregs or administration of exogenous IL-2 had similar effects.

        (1) Zhang C (2) Chien C (3) Jurgaityt_ E (4) Sakiyama K (5) Bockman A (6) Jo Y (7) Lee S (8) Silveria S (9) Andrews E (10) Mende A (11) Zhang L (12) Garcia KC (13) Wagner A (14) DuPage M (15) Raulet D

        Science immunology

        Zhang et al. found that intratumoral depletion of Tregs elicited potent antitumor NK cell responses that controlled MHC-I-deficient and even MHC-I-proficient cancers expressing sufficient NKG2D ligands. This effect was dependent on cDC2-mediated activation of CD4+ T cells and their subsequent production of IL-2, which directly enhanced NK cell activation and cytotoxic potential. Antibody-mediated depletion of intratumoral Tregs or administration of exogenous IL-2 had similar effects.

        ABSTRACT: Cancer cells frequently lose major histocompatibility complex class I (MHC I) to evade CD8 T cell recognition. Natural killer (NK) cells are poised to target MHC I-deficient cancer cells, but MHC I loss alone is often insufficient to unleash fully effective NK cell responses. Here, we show that selective intratumoral (IT) ablation of regulatory T cells (T(reg) cells) elicited potent antitumor NK cell responses that controlled MHC I-deficient and even MHC I(+) cancers that expressed NKG2D ligands. T(reg) cells controlled the activation, maturation, and antitumor cytotoxic activity of NK cells within the tumor microenvironment. Mechanistically, depletion of IT-T(reg) cells relieved the inhibition of cDC2-dependent induction of IL-2 production by conventional CD4 T cells that was necessary for NK cell activation. Systemically administered antibodies that selectively depleted IT-T(reg) cells similarly empowered NK cell-dependent tumor control. These findings expand the breadth of T(reg) cell-mediated cancer immunosuppression to encompass antitumor NK cells and suggest that therapeutic targeting of T(reg) cells in tumors can control CD8 T cell-resistant cancers.

        Author Info: (1) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (2) Department of Electric

        Author Info: (1) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (2) Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA. Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (3) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (4) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (5) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (6) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (7) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (8) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (9) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (10) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (11) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (12) Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Palo Alto, CA 94305, USA. (13) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA. Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (14) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. (15) Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

        Citation: Sci Immunol 2026 Apr 10 11:eadx4411 Epub04/10/2026

        Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/41961946

        Tags:

        Debio 1562M CD37-targeting ADC is highly active and well tolerated in preclinical models of AML and MDS Spotlight 

        (1) Marx L (2) Hue-Perron J (3) Monjardet A (4) Vigano S (5) Chardonnens C (6) Morse K (7) Artiga E (8) Roubaudi-Fraschini MC (9) Wuttke R (10) Colombo R (11) Larkin K (12) Ivanschitz L

        Cell reports. Medicine

        Addressing the need for superior toxin delivery and safety for AML and MDS therapies, Marx et al. developed Debio 1562M, a next-generation ADC targeting CD37, which is broadly expressed on AML and MDS blasts. Debio 1562M (with a drug [DM1]-to-naratuximab ratio of 8, and a cathepsin-cleavable linker) was efficiently internalized and killed blast cells in blood and bone marrow. In multiple models, Debio 1562M outperformed standard-of-care treatments, and demonstrated broad and efficient anti-leukemic activity on all AML subtypes. Compared to 1st generation CD37 ADC, Debio 1562M had an improved toxicity profile in mice, and is in a phase 1 trial for r/r AML and high-risk MDS.

        Contributed by Katherine Turner

        (1) Marx L (2) Hue-Perron J (3) Monjardet A (4) Vigano S (5) Chardonnens C (6) Morse K (7) Artiga E (8) Roubaudi-Fraschini MC (9) Wuttke R (10) Colombo R (11) Larkin K (12) Ivanschitz L

        Cell reports. Medicine

        Addressing the need for superior toxin delivery and safety for AML and MDS therapies, Marx et al. developed Debio 1562M, a next-generation ADC targeting CD37, which is broadly expressed on AML and MDS blasts. Debio 1562M (with a drug [DM1]-to-naratuximab ratio of 8, and a cathepsin-cleavable linker) was efficiently internalized and killed blast cells in blood and bone marrow. In multiple models, Debio 1562M outperformed standard-of-care treatments, and demonstrated broad and efficient anti-leukemic activity on all AML subtypes. Compared to 1st generation CD37 ADC, Debio 1562M had an improved toxicity profile in mice, and is in a phase 1 trial for r/r AML and high-risk MDS.

        Contributed by Katherine Turner

        ABSTRACT: The leukocyte antigen CD37 is broadly expressed on acute myeloid leukemia (AML) blasts and associated with poor prognosis. We demonstrate that myelodysplastic syndrome (MDS) cells also express CD37, and both AML and MDS cells have favorable internalization properties of this receptor. Debio 1562M is a next-generation antibody-drug conjugate (ADC) that targets CD37 and is optimized to deliver more toxins to tumor cells than the first-generation ADC Debio 1562, while maintaining a good safety profile. Preclinically, Debio 1562M showed robust anti-leukemic activity in AML and MDS primary samples and in AML xenograft models, irrespective of disease stage or genotype. Debio 1562M was able to target leukemic stem cells in vitro and significantly decrease tumor burden in blood and bone marrow, resulting in survival prolongation compared with standard-of-care treatments. These data demonstrate that CD37 is a relevant target for both indications and that Debio 1562M is a promising therapeutic candidate.

        Author Info: (1) Debiopharm Research and Manufacturing SA, 1920 Martigny, Switzerland. (2) Debiopharm International SA, 1006 Lausanne, Switzerland. (3) Debiopharm International SA, 1006 Lausann

        Author Info: (1) Debiopharm Research and Manufacturing SA, 1920 Martigny, Switzerland. (2) Debiopharm International SA, 1006 Lausanne, Switzerland. (3) Debiopharm International SA, 1006 Lausanne, Switzerland. (4) Debiopharm Research and Manufacturing SA, 1920 Martigny, Switzerland. (5) Debiopharm Research and Manufacturing SA, 1920 Martigny, Switzerland. (6) Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. (7) Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. (8) Debiopharm International SA, 1006 Lausanne, Switzerland. (9) Debiopharm International SA, 1006 Lausanne, Switzerland. (10) Debiopharm International SA, 1006 Lausanne, Switzerland. (11) Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. (12) Debiopharm International SA, 1006 Lausanne, Switzerland. Electronic address: lisa.ivanschitz@debiopharm.com.

        Citation: Cell Rep Med 2026 Apr 20 102749 Epub04/20/2026

        Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42013843

        Tags:

        Spleen-targeted neoantigen mRNA vaccine induces ISG15+ CD8+ T cell-mediated tertiary lymphoid structure formation in hepatocellular carcinoma

        Spotlight 

        (1) Lin X (2) Chen G (3) Tang R (4) Wu M (5) Zhang D (6) Lin F (7) Guan J (8) Yang J (9) Dong X (10) Zheng X (11) Qiu L (12) Yu H (13) Cai Z (14) Liu X

        Cell reports. Medicine

        Lin et al. engineered a spleen-targeted neoantigen mRNA vaccine (STNvac) using a two-component LNP formulation that selectively delivered mRNA to splenic DCs and prompted robust neoantigen-specific CD8+ T cell response in an orthotopic Hepa1-6 HCC model. STNvac induced a distinct ISG15+ CD8+ T cell subset with enhanced cytotoxicity that mediated antigen-specific tumor clearance. Single-cell and spatial analyses showed interaction between ISG15+ CD8+ T cells and intratumoral APCs via a GZMA–F2R axis, which drove ISG15+ CD8+ T cell activation, proliferation, and organization into TLSs in human and mouse HCC specimens.

        Contributed by Shishir Pant

        (1) Lin X (2) Chen G (3) Tang R (4) Wu M (5) Zhang D (6) Lin F (7) Guan J (8) Yang J (9) Dong X (10) Zheng X (11) Qiu L (12) Yu H (13) Cai Z (14) Liu X

        Cell reports. Medicine

        Lin et al. engineered a spleen-targeted neoantigen mRNA vaccine (STNvac) using a two-component LNP formulation that selectively delivered mRNA to splenic DCs and prompted robust neoantigen-specific CD8+ T cell response in an orthotopic Hepa1-6 HCC model. STNvac induced a distinct ISG15+ CD8+ T cell subset with enhanced cytotoxicity that mediated antigen-specific tumor clearance. Single-cell and spatial analyses showed interaction between ISG15+ CD8+ T cells and intratumoral APCs via a GZMA–F2R axis, which drove ISG15+ CD8+ T cell activation, proliferation, and organization into TLSs in human and mouse HCC specimens.

        Contributed by Shishir Pant

        ABSTRACT: The efficacy of neoantigen vaccine for advanced hepatocellular carcinoma (HCC) is limited largely due to insufficient T cell mobilization and activation. Herein, we develop a spleen-targeted neoantigen mRNA vaccine (STNvac) with highly efficient spleen-selective mRNA transfection. Using a three-dose vaccination regimen, STNvac demonstrates remarkable therapeutic efficacy in orthotopic HCC model with a high likelihood of complete tumor regression and significantly improved survival rates (p < 0.0001). Notably, we identify a distinct ISG15(+) CD8(+) T cell population as crucial mediators of STNvac-induced immunity with potent antigen-processing and cytotoxic capacities. Intriguingly, STNvac promotes the formation of tertiary lymphoid structures (TLSs) through GZMA-F2R-mediated interactions between ISG15(+) CD8(+) T cells and antigen-presenting cells (APCs), which is also confirmed in HCC patients. Taken together, our findings demonstrate the potent antitumor efficacy of spleen-targeted mRNA vaccine and reveal its underlying immune cell interactive mechanisms, presenting high potential for clinical translation.

        Author Info: (1) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 35000

        Author Info: (1) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (2) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (3) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (4) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (5) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (6) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (7) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (8) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (9) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (10) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (11) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. (12) State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. (13) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. Electronic address: caizhixiong1985@163.com. (14) The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350007, P.R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, Fujian 350116, P.R. China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian 350007, P.R. China. Electronic address: xiaoloong.liu@gmail.com.

        Citation: Cell Rep Med 2026 Apr 20 102754 Epub04/20/2026

        Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42013842

        Tags:
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