IL-17 effect on tumor progression may depend on particular IL-17 receptors subunit expression on tumor cells and effects on antitumor immunity

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

Congreso; Reunión de Sociedades de Biociencias 2020; 2020

The role of IL-17 signaling in the tumor progression is controversial. Several reports indicate that IL-17 sustain, directly and indirectly, tumor growth and immune-escape. However, IL-17also supportsanti-tumoral immunity by potentiating CD8+ T and NK cell responses. Our aim is to determine the role of IL-17-signaling in tumor progression dissecting pro- and anti-tumoral effects. First, we evaluated IL-17 receptor (IL-17Rs) expression in melanoma (B16-SIY) and thymoma (EL4-SIY) tumor cells. While both cells expressed varied amounts of IL-17RA and IL-17RD transcripts, IL-17RC was detected only in B16-SIY. According to the different IL-17Rs expression profiles, exposure to IL-17A in vitro resulted in different outcomes. B16-SIY showed an increase in the amounts of transcripts encoding pro-inflammatory mediators (VEGF, HIF1a and N-cadherin, p<0.05) and no change in others (FGF1, MMP2, MMP9, PDL1). Remarkably, EL4-SIY only showed an increase in the amounts of PDL1(p<0.001). Then, we evaluated tumor growth in vivo in IL-17-signaling-deficient mice and in WT mice to determine the overall role of IL-17 in tumor progression. Interestingly, compared to WT controls, IL-17 deficient mice showed augmented B16-SIY tumor volume (p<0.05,18dpi) butdiminished EL4-SIY tumor volume (p<0.001,21dpi) at several days post-injection (dpi) . Finally, we evaluated tumor-infiltrating lymphocytes (TILs) in B16-SIY and EL4-SIY tumors from both mousestrains. The percentages of total and SIY- specific CD8+ cells within TILs obtained at day 18 or 21pi from both tumors were diminished in IL-17 deficient mice compared to WT controls(p<0.05), suggesting that IL-17 signaling is required for the proper development of antitumor CD8+T cell immunity irrespective to its global effect on tumor progression. Our results highlight that IL-17-signaling role in overall tumor progression may be influenced by tumor profiles of IL-17R subunit expression together with IL-17 effects on antitumor inmunity.