title: IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway.
abstract: Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role in cancer remains to be further explored. IL-17 has been shown to be elevated in several types of cancer, but how it might contribute to tumor growth is still unclear. We show that growth of B16 melanoma and MB49 bladder carcinoma is reduced in IL-17(-/-) mice but drastically accelerated in IFN-gamma(-/-) mice, contributed to by elevated intratumoral IL-17, indicating a role of IL-17 in promoting tumor growth. Adoptive transfer studies and analysis of the tumor microenvironment suggest that CD4(+) T cells are the predominant source of IL-17. Enhancement of tumor growth by IL-17 involves direct effects on tumor cells and tumor-associated stromal cells, which bear IL-17 receptors. IL-17 induces IL-6 production, which in turn activates oncogenic signal transducer and activator of transcription (Stat) 3, up-regulating prosurvival and proangiogenic genes. The Th17 response can thus promote tumor growth, in part via an IL-6-Stat3 pathway.
authors: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute at City of Hope Medical Center, Duarte, CA 91010, USA.
authors: Lin
authors: L
authors: Wang
authors: Tangsheng
authors: T
authors: Yi
authors: Marcin
authors: M
authors: Kortylewski
authors: Drew M
authors: DM
authors: Pardoll
authors: Defu
authors: D
authors: Zeng
authors: Hua
authors: H
authors: Yu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D007371:Interferon-gamma