IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2

• Published in: Scientific reports Vol. 3; no. 1; p. 3456
• Main Authors: Cochaud, Stéphanie, Giustiniani, Jérôme, Thomas, Clémence, Laprevotte, Emilie, Garbar, Christian, Savoye, Aude-Marie, Curé, Hervé, Mascaux, Corinne, Alberici, Gilles, Bonnefoy, Nathalie, Eliaou, Jean-François, Bensussan, Armand, Bastid, Jeremy
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 09.12.2013
• Subjects: Antibodies; Antineoplastic Agents - pharmacology; Biopsy; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Chemoresistance; Chemotherapy; Drug Resistance, Neoplasm; Extracellular signal-regulated kinase; Female; Humans; Inflammation; Interleukin-17 - biosynthesis; Interleukin-17 - genetics; Leukocyte migration; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; MAP kinase; MAP Kinase Signaling System - drug effects; Medical prognosis; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Receptors, Estrogen - metabolism; Taxoids - pharmacology; Tumor cell lines; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep03456

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.