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

ARAUJO FURLÁN CL; BOSSIO SN; MONTES CL; RODRIGUEZ C; CANALE FP; BECCARIA CG; ACOSTA RODRIGUEZ EV; TOSELLO BOARI J; BOCCARDO S; GRUPPI A

Congreso; LXVII Reunión Anual de la SAI.; 2019

IL-17 role in cancer remains unclear. Thus, IL-17 may play a pro-tumoral role 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 expressed different amounts of IL-17RA and IL-17RD transcripts; IL-17RC transcript was not detected only in EL4-SIY and C1498-SIY cells. Therefore, we evaluated tumor cell response after IL-17A or IL-17F exposure. B16-SIY and MC57-SIY up-regulated transcripts levels of pro-tumoral VEGF, HIF1a, FGF-1, MMP2, MMP9 and CDH2, while MCA-OVA down-regulated expression of all, consistent with augmented IL-17RD expression in MCA-OVA cells, that may inhibit IL-17/IL-17RA-RC signaling. No changes in transcripts levels after IL-17A/F exposure was detected in EL4-SIY and C1498-SIY, consistent with lack of IL-17RC expression. Finally, we evaluated tumor progression in IL-17-signaling-deficient mice, B16-SIY and MC57-SIY tumor volume was augmented several days post-injection compared to WT controls. No changes in MCA-OVA tumor volume among strains was found. Interesting, IL-17-deficient mice showed diminished EL4-SIY and C1498-SIY tumor volume compared to WT. Our results highlight that IL-17-signaling role in overall tumor progression is dependent of the balance between tumor cell IL-17Rs expression an IL-17 effect on tumor microenviroment. Further research will determine possible IL-17 targets that shape the overall progression in each tumor type.