title: Interleukin-33 in tumorigenesis, tumor immune evasion, and cancer immunotherapy.
abstract: Interleukin-33 (IL-33) is a member of the IL-1 gene family and mainly expressed in the nucleus of tissue lining cells, stromal cells, and activated myeloid cells. IL-33 is considered a damage-associated molecular pattern (DAMP) molecule and plays an important role in many physiological and pathological settings such as tissue repair, allergy, autoimmune disease, infectious disease, and cancer. The biological functions of IL-33 include maintaining tissue homeostasis, enhancing type 1 and 2 cellular immune responses, and mediating fibrosis during chronic inflammation. IL-33 exerts diverse functions through signaling via its receptor ST2, which is expressed in many types of cells including regulatory T cells (Treg), group 2 innate lymphoid cells (ILC2s), myeloid cells, cytotoxic NK cells, Th2 cells, Th1 cells, and CD8(+) T cells. Tumor development results in downregulation of IL-33 in epithelial cells but upregulation of IL-33 in the tumor stroma and serum. The current data suggest that IL-33 expression in tumor cells increases immunogenicity and promotes type 1 antitumor immune responses through CD8(+) T cells and NK cells, whereas IL-33 in tumor stroma and serum facilitates immune suppression via Treg and myeloid-derived suppressor cell (MDSC). Understanding the role of IL-33 in cancer immunobiology sheds lights on targeting this cytokine for cancer immunotherapy.
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15261, USA. binfeng@pitt.edu.|University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. binfeng@pitt.edu.
authors.forename: Binfeng
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D000072645:Cancer-Associated Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007113:Immunity, Innate; D007157:Immunologic Surveillance; D007167:Immunotherapy; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000067596:Interleukin-33 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology*
chemical_list: D000067596:Interleukin-33
keywords: CD8 T cell; Cancer immunotherapy; Interleukin-33; MDSC; Tumorigenesis