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

RODRIGEZ, CONSTANZA; FURLAN, CINTIA L. ARAUJO; BOCCARDO, SANTIAGO; BOSSIO, SABRINA N.; JIMENA TOSELLO BOARI; CANALE, FERNANDO P.; BECCARIA, CRISTIAN; GRUPPI, ADRIANA; MONTES, CAROLINA L.; RODRÍGUEZ, EVA V. ACOSTA

Congreso; Reunión Anual de Sociedades de Biociencias. SAIC - SAI - SAFIS; 2020

The role of IL-17 signaling in the tumor progression is controversial. Several reportsindicate that IL-17 sustain, directly and indirectly, tumor growth and immune-escape.However, IL-17also supports anti-tumoral immunity by potentiating CD8+ T and NKcell responses. Our aim is to determine the role of IL-17-signaling in tumorprogression dissecting pro- and anti-tumoral effects. First, we evaluated IL-17receptor (IL-17Rs) expression in melanoma (B16-SIY) and thymoma (EL4-SIY)tumor cells. While both cells expressed varied amounts of IL-17RA and IL-17RDtranscripts, IL-17RC was detected only in B16-SIY. According to the different IL17Rs expression profiles, exposure to IL-17A in vitro resulted in different outcomes.B16-SIY showed an increase in the amounts of transcripts encoding proinflammatory mediators (VEGF, HIF1a and N-cadherin, p<0.05) and no change inothers (FGF1, MMP2, MMP9, PDL1). Remarkably, EL4-SIY only showed anincrease in the amounts of PDL1(p<0.001). Then, we evaluated tumor growth in vivoin IL-17-signaling-deficient mice and in WT mice to determine the overall role of IL17 in tumor progression. Interestingly, compared to WT controls, IL-17 deficient miceshowed augmented B16-SIY tumor volume (p<0.05,18dpi) but diminished EL4-SIYtumor volume (p<0.001,21dpi) at several days post-injection (dpi) . Finally, weevaluated tumor-infiltrating lymphocytes (TILs) in B16-SIY and EL4-SIY tumors fromboth mouse strains. The percentages of total and SIY- specific CD8+ cells withinTILs obtained at day 18 or 21pi from both tumors were diminished in IL-17 deficientmice compared to WT controls(p<0.05), suggesting that IL-17 signaling is requiredfor the proper development of antitumor CD8+T cell immunity irrespective to itsglobal effect on tumor progression. Our results highlight that IL-17-signaling role inoverall tumor progression may be influenced by tumor profiles of IL-17R subunitexpression together with IL-17 effects on antitumor inmunity.