title: IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses.
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.
authors: Department 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.
authors: Xuefeng
authors: X
authors: Wang
authors: Department 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.
authors: Xin
authors: X
authors: Zhao
authors: Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors: Chao
authors: C
authors: Feng
authors: Department 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.
authors: Aliyah
authors: A
authors: Weinstein
authors: Department 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.
authors: Rui
authors: R
authors: Xia
authors: Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors: Wen
authors: W
authors: Wen
authors: Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors: Quansheng
authors: Q
authors: Lv
authors: Department 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.
authors: Shuting
authors: S
authors: Zuo
authors: Department of Pulmonary Tuberculosis, The Affiliated Hospital for Infectious Diseases of Soochow University, Suzhou 215007, China.
authors: Peijun
authors: P
authors: Tang
authors: Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; School of Medicine, Tsinghua University, Peking 100084, China.
authors: Xi
authors: X
authors: Yang
authors: Department 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.
authors: Xiaojuan
authors: X
authors: Chen
authors: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
authors: Hongrui
authors: H
authors: Wang
authors: Department 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.
authors: Shayang
authors: S
authors: Zang
authors: Department of Anesthesiology, University of Pittsburgh Medical Center, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors: Lindsay
authors: L
authors: Stollings
authors: Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors: Timothy L
authors: TL
authors: Denning
authors: Department of Tumor Biotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
authors: Jingting
authors: J
authors: Jiang
authors: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Research and Development, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh PA 15240, USA.
authors: Jie
authors: J
authors: Fan
authors: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Guangbo
authors: G
authors: Zhang
authors: Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors: Xueguang
authors: X
authors: Zhang
authors: Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors: Yibei
authors: Y
authors: Zhu
authors: Department 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.
authors: Walter
authors: W
authors: Storkus
authors: Department 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.
authors: Binfeng
authors: B
authors: Lu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007375:Interleukin-1 / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C508589:IL36G protein, human; D007375:Interleukin-1; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12