title: IL-17A produced by γδ T cells promotes tumor growth in hepatocellular carcinoma.
abstract: Interleukin (IL)-17A is expressed in the tumor microenvironment where it appears to contribute to tumor development, but its precise role in tumor immunity remains controversial. Here, we report mouse genetic evidence that IL-17A is critical for tumor growth. IL-17A-deficient mice exhibited reduced tumor growth, whereas systemic administration of recombinant mouse IL-17A promoted the growth of hepatocellular carcinoma. The tumor-promoting effect of IL-17A was mediated through suppression of antitumor responses, especially CD8(+) T-cell responses. Furthermore, we found that IL-17A was produced mainly by Vγ4 γδ T cells, insofar as depleting Vγ4 γδ T cells reduced tumor growth, whereas adoptive transfer of Vγ4 γδ T cells promoted tumor growth. Mechanistic investigations showed that IL-17A induced CXCL5 production by tumor cells to enhance the infiltration of myeloid-derived suppressor cells (MDSC) to tumor sites in a CXCL5/CXCR2-dependent manner. IL-17A also promoted the suppressive activity of MDSC to reinforce suppression of tumoral immunity. Moreover, we found that MDSC could induce IL-17A-producing γδ T cells via production of IL-1β and IL-23. Conversely, IL-17A could also enhance production of IL-1β and IL-23 in MDSC as a positive feedback. Together, our results revealed a novel mechanism involving cross-talk among γδ T cells, MDSCs, and tumor cells through IL-17A production. These findings offer new insights into how IL-17A influences tumor immunity, with potential implications for the development of tumor immunotherapy.
authors: Authors' Affiliations: Laboratory of Cellular and Molecular Tumor Immunology, Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University; Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou; Department of Basic Medical Science, Key Lab of Inflammation and Immunoregulation, School of Medicine, Hangzhou Normal University, Hangzhou, PR China; and Department of Immunology, MD Anderson Cancer Center, Houston, Texas.
authors: Shoubao
authors: S
authors: Ma
authors: Qiao
authors: Q
authors: Cheng
authors: Yifeng
authors: Y
authors: Cai
authors: Huanle
authors: H
authors: Gong
authors: Yan
authors: Y
authors: Wu
authors: Xiao
authors: X
authors: Yu
authors: Liyun
authors: L
authors: Shi
authors: Depei
authors: D
authors: Wu
authors: Chen
authors: C
authors: Dong
authors: Haiyan
authors: H
authors: Liu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000502:physiology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D023063:Receptors, Interleukin-8B / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023063:Receptors, Interleukin-8B