IL-17 EFFECT ON TUMOR PROGRESSION MAY DEPEND ON PARTICULAR IL-17 RECEPTORS SUBUNIT EXPRESSION ON TUMOR CELLS AND EFFECTS ON ANTITUMOR IMMUNITY

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

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) andthymoma (EL4-SIY) tumor cells. While both cells expressed variedamounts of IL-17RA and IL-17RD transcripts, IL-17RC was detected only in B16-SIY. According to the different IL-17Rs expressionprofiles, exposure to IL-17A in vitro resulted in different outcomes.B16-SIY showed an increase in the amounts of transcripts encodingpro-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-deficientmice and in WT mice to determine the overall role of IL-17 in tumorprogression. Interestingly, compared to WT controls, IL-17 deficientmice showed augmented B16-SIY tumor volume (p<0.05,18dpi) butdiminished EL4-SIY tumor volume (p<0.001,21dpi) at several dayspost-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 withinTILs obtained at day 18 or 21pi from both tumors were diminished inIL-17 deficient mice compared to WT controls(p<0.05), suggestingthat IL-17 signaling is required for the proper development of antitumor CD8+T cell immunity irrespective to its global effect on tumorprogression. Our results highlight that IL-17-signaling role in overalltumor progression may be influenced by tumor profiles of IL-17Rsubunit expression together with IL-17 effects on antitumor inmunity.Key words: IL-17, IL-17R, anti-tumoral immunity,