IL-17 and Triple Negative Breast Cancer

Rouvier et al. [1] discovered interleukin 17 (IL-17) in 1993 and originally termed it CTLA-8 from their experiences on rodent hybridoma cDNA [1]. Later, other cytokines resembling it were discovered to form the IL-17 family, which comprises 6 members from its archetype IL-17 or IL-17A, to IL-17F. IL-17 is secreted mainly by T helper lymphocytes as a homodimer or a heterodimer, but secretion by other cells like neutrophils, TCR-γδ lymphocytes, CD8+ T cells, natural killers and mast cells has also been reported [2]. The different isoforms of IL-17 have pleiotropic functions and signal through a ubiquitous transmembrane receptor, the IL-17R of which 5 subunits exists: IL-17RA, IL-17RB, IL-17RC, IL-17RD, IL-17RE. The importance of the Th17 axis has been extensively studied and demonstrated in chronic inflammatory disease of the skin or the joints. Antibodies directed against IL-17 or IL17R is clinically effective and has shown therapeutic responses never seen before in psoriasis [3]. Besides, several studies have reported IL-17 and IL-17R to play roles in diverse cancer types though some results are conflicting [4]. Triple negative breast cancer (TNBC) is a very aggressive form of breast cancer (BC) characterized by a young age of patients, frequent relapse, and poor prognosis. Similarly as other cancer types, TNBC builds on inflammation in the tumour microenvironment to progress, grow and metastasize. Since they lack expression of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), systemic treatments are limited to chemotherapy to which TNBC rapidly become resistant [5]. Therefore, IL-17 has been investigated in TNBC as a potential target for anti-cancer treatment and several studies have already highlighted its pro-tumoral functions.