title: Targeting of interleukin (IL)-17A inhibits PDL1 expression in tumor cells and induces anticancer immunity in an estrogen receptor-negative murine model of breast cancer.
abstract: The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1-PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated. Therefore, we assessed whether IL-17A promotes PDL1 expression in tumor cells and whether targeting of IL-17A could inhibit ER-negative breast cancer progression in a murine model. Our study revealed that IL-17A promoted PDL1 expression in human and mouse cells. In the murine cancer model, targeting of IL-17A inhibited PDL1 expression in the tumor microenvironment, decreased the percentage of Treg cells in tumor-infiltrating lymphocytes, and promoted CD4+ and CD8+ T cells to secrete interferon gamma. More importantly, treatment with combined anti-IL-17A and anti-PDL1 antibodies enhanced antitumor effects in favor of tumor eradication. Thus, our study established a pro-tumor role of IL-17A in promoting tumor immune escape and supports the development of a novel cytokine immunotherapy against breast cancer.
authors.affiliation: Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, P. R. China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Ma
authors.affiliation: Clinical School of Hubei University of Chinese Medicine, Hubei University of Chinese medicine, Wuhan, Hubei, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Microbiology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, P. R. China.
authors.forename: Zhuang-Wei
authors.initials: ZW
authors.lastname: Lv
authors.affiliation: Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, P. R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, P. R. China.
authors.forename: Jiru
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000172:deficiency*; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D019139:Tumor Escape / Q000187:drug effects; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C498919:Cd274 protein, mouse; C573415:IFNG protein, human; C508717:IL17A protein, human; C098680:Il17a protein, mouse; D020381:Interleukin-17; D011960:Receptors, Estrogen; D007371:Interferon-gamma
keywords: breast cancer; estrogen receptor; immunotherapy; interleukin-17; programmed death ligand 1