Expression profile of IL-17 receptor subunits on murine cancer cells determines their response to IL-17A/F signaling

C RODRIGUEZ; J TOSELLO BOARI; C ARAUJO FURLAN; F CANALE; S BOCCARDO; S BOSSIO; C BECCARIA; A GRUPPI; CL MONTES; EV ACOSTA RODRIGUEZ

Tucumán

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

IL-17 may have pro-tumoral effects by sustaining tumor cell growth or may support antitumoral immunity by potentiating CD8+ T cell and NK cell responses. Our aim is to determine IL-17-signaling role in tumor progression dissecting pro- and anti-tumoral effects. Therefore, we evaluated IL-17 receptor (IL-17Rs) expression in different murine tumor cells: melanoma (B16-SIY), fibrosarcoma (MC57-SIY and MCA-OVA), lymphoma (EL4-SIY) and acute myeloid leukemia (C1498-SIY). While all cells evaluated had different amounts of IL-17RA and IL-17RD transcripts; IL-17RC transcript was detected only in B16-SIY, MC57-SIY and MCA-OVA cells. Exposure to IL-17A or IL-17F in vitro resulted in an increase in the amounts of transcripts encoding pro-tumoral mediators (VEGF, HIF1a, FGF-1, MMP2, MMP9 and CDH2) in B16-SIY and MC57-SIY. MCA-OVA also responded to these cytokines by down-regulating these mediators, consistent with its higher IL-17RD expression, a subunit reported to inhibit IL-17/IL-17RA-RC signaling. Remarkably, no response to IL-17A/F was detected in EL4-SIY and C1498-SIY that may be associated to the lack of IL-17RC expression. Finally, we evaluated tumor progression in IL-17-signaling-deficient in comparison to WT mice and determined that tumor volume was augmented at several days post-injection of B16-SIY and MC57-SIY, showed no changes upon injection of MCA-OVA and, interestingly was diminished along progression of EL4-SIY and C1498-SIY tumors. Our results highlight that IL-17-signaling role in overall tumor progression may be influenced by particular profiles of IL-17R subunit expression together with IL-17 effects on tumor microenvironment. Further research will determine possible IL-17 targets to shape the overall progression in different tumor types.