ArticleCancer cell2015
IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses.
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Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76citing papers in PubMed
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76 citing papers in PubMed, 109 citations in OpenAlex.
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- γδ T cells: bridging innate and adaptive immunity in development, tissue residency, and disease.Frontiers in immunology · 2026Review
- Specific inhibitor to KRASJournal for immunotherapy of cancer · 2025Article
- Enhanced IL36RN Expression and Its Association With Immune Microenvironment Predicts Poor Prognosis in Gastric Cancer.Cancer medicine · 2025Article
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- Advances of oncolytic vaccinia viruses armed with interleukin in tumor therapy.Frontiers in oncology · 2025Review
- Interleukin 1 family dysregulation in serum and peritoneal fluid of ovarian cancer patients - potential clinical implications.Frontiers in oncology · 2025Article
- Breaking barriers: enhancing CAR-armored T cell therapy for solid tumors through microenvironment remodeling.Frontiers in immunology · 2025Review
- Circular RNA circPHLPP2 promotes tumor growth and anti-PD-1 resistance through binding ILF3 to regulate IL36γ transcription in colorectal cancer.Molecular cancer · 2024Article
- IL-36 Gamma: A Novel Adjuvant Cytokine Enhancing Protective Immunity Induced by DNA Immunization with TGIST and TGNSM AgainstMicroorganisms · 2024Article
- Oncolytic virus and tumor-associated macrophage interactions in cancer immunotherapy.Clinical and experimental medicine · 2024Review
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- Enhanced cellular therapy: revolutionizing adoptive cellular therapy.Experimental hematology & oncology · 2024Review
- Recent progress in combination therapy of oncolytic vaccinia virus.Frontiers in immunology · 2024Review
- Arming CAR-T cells with cytokines and more: Innovations in the fourth-generation CAR-T development.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Autonomous IL-36R signaling in neutrophils activates potent antitumor effector functions.The Journal of clinical investigation · 2023Article
- New insights on IL‑36 in intestinal inflammation and colorectal cancer (Review).Experimental and therapeutic medicine · 2023Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 2 countries.
Xuefeng WangDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Biochemistry and Molecular Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Xin ZhaoDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Chao FengDepartment of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Aliyah WeinsteinDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Dermatology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Rui XiaDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Wen WenDepartment of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Quansheng LvDepartment of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Shuting ZuoDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Surgery, The Second Hospital of Jilin University, Changchun 130041, China.
Peijun TangDepartment of Pulmonary Tuberculosis, The Affiliated Hospital for Infectious Diseases of Soochow University, Suzhou 215007, China.
Xi YangDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; School of Medicine, Tsinghua University, Peking 100084, China.
Xiaojuan ChenDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Hongrui WangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Shayang ZangDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Lindsay StollingsDepartment of Anesthesiology, University of Pittsburgh Medical Center, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA.
Timothy L DenningCenter for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Jingting JiangDepartment of Tumor Biotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Jie FanDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Research and Development, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh PA 15240, USA.
Guangbo ZhangJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Xueguang ZhangDepartment of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Yibei ZhuDepartment of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Walter StorkusDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Dermatology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Binfeng LuDepartment of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA 15261, USA. Electronic address: binfeng@pitt.edu.
University of Pittsburgh · USSoochow University · CNGeorgia State University · USUniversity of Pittsburgh Medical Center · USXiamen University · CN
Funding
UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9MUniversity of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8MWILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6MRPCI-UPCI Ovarian Cancer SPOREP50CA159981 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B. · 2013 to 2025
$19.6MAutoimmunity and Immunopathology Training ProgramT32AI089443 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHLOMCHIK, MARK J · 2010 to 2024
$6.6MResearch Training in Anesthesiology and Pain MedicineT32GM075770 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YAN XU · 2007 to 2026
$4.8MCombinational Immunotherapy Targeting the Melanoma-Associated VasculatureR01CA169118 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STORKUS, WALTER J. · 2012 to 2016
$2.1MCellular and molecular mechanisms underlying IL-33-mediated anti-tumor immunityR21CA167229 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LU, BINFENG · 2013 to 2014
$360kNCATS NIH HHS UL1 TR000005NCATS NIH HHS UL1TR000005NCI NIH HHS 1P50 CA097190NCI NIH HHS P50 CA097190NCI NIH HHS P50 CA159981NCI NIH HHS P50CA159981NCI NIH HHS R01 CA169118NCI NIH HHS R21 CA167229NCI NIH HHS R21CA167229NCRR NIH HHS UL1 RR024153NIAID NIH HHS T32 AI089443NIGMS NIH HHS T32 GM075770NIGMS NIH HHS T32GM075770
Abstract
Cytokines play a pivotal role in regulating tumor immunogenicity and antitumor immunity. IL-36γ is important for the IL-23/IL-17-dominated inflammation and anti-BCG Th1 immune responses. However, the impact of IL-36γ on tumor immunity is unknown. Here we found that IL-36γ stimulated CD8(+) T cells, NK cells, and γδ T cells synergistically with TCR signaling and/or IL-12. Importantly, IL-36γ exerted profound antitumor effects in vivo and transformed the tumor microenvironment in favor of tumor eradication. Furthermore, IL-36γ strongly increased the efficacy of tumor vaccination. Moreover, IL-36γ expression inversely correlated with the progression of human melanoma and lung cancer. Our study establishes a role of IL-36γ in promoting antitumor immune responses and suggests its potential clinical translation into cancer immunotherapy.
Indexed as
AnimalsAntigens, NeoplasmCancer VaccinesCD8-Positive T-LymphocytesHumansImmunotherapyInterleukin-1Interleukin-12Killer Cells, NaturalLung NeoplasmsMelanoma, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLReceptors, Antigen, T-Cell, gamma-deltaTumor Cells, CulturedAntigens, NeoplasmCancer VaccinesIL36G protein, humanInterleukin-1Interleukin-12Receptors, Antigen, T-Cell, gamma-delta
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