title: IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2.
abstract: The proinflammatory cytokine Interleukin 17A (hereafter named IL-17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(-) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems mainly associated to ER(-) and triple negative/basal-like tumors. Isolation of tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that these cells secreted significant amounts of IL-17A. We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel. We also confirmed here that recombinant IL-17A stimulates migration and invasion of breast cancer cells as previously reported. Importantly, TILs also induced tumor cell proliferation, chemoresistance and migration and treatment with IL-17A-neutralizing antibodies abrogated these effects. Altogether these results demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a subset of breast cancers. Therefore, IL-17A appears as potential therapeutic target for breast cancer.
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 976; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Immunologie Dermatologie & Oncologie, F-75475, Paris, France [2].
authors: Stéphanie
authors: S
authors: Cochaud
authors: Jérôme
authors: J
authors: Giustiniani
authors: Clémence
authors: C
authors: Thomas
authors: Emilie
authors: E
authors: Laprevotte
authors: Christian
authors: C
authors: Garbar
authors: Aude-Marie
authors: AM
authors: Savoye
authors: Hervé
authors: H
authors: Curé
authors: Corinne
authors: C
authors: Mascaux
authors: Gilles
authors: G
authors: Alberici
authors: Nathalie
authors: N
authors: Bonnefoy
authors: Jean-François
authors: JF
authors: Eliaou
authors: Armand
authors: A
authors: Bensussan
authors: Jeremy
authors: J
authors: Bastid
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D011960:Receptors, Estrogen / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D020381:Interleukin-17; D011960:Receptors, Estrogen; D043823:Taxoids; D000077143:Docetaxel; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3