EXPRESSION PROFILE OF IL-17 RECEPTOR SUBUNITS ON MURINE CANCER CELLS DETERMINES THEIR RESPONSE TO IL-17A/F SIGNALING.

CONSTANZA RODRIGUEZ; JIMENA TOSELLO BOARI; CINTIA ARAUJO FURLAN; FERNANDO PABLO CANALE; SANTIAGO BOCCARDO; SABRINA NOEMÍ BOSSIO; CRISTIAN GABRIEL BECCARIA; ADRIANA GRUPPI; CAROLINA LUCÍA MONTES; EVA VIRGINIA ACOSTA RODRÍGUEZ

Tucumán

Congreso; Reunion 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 antitumoralimmunity 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, weevaluated 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-17RCtranscript was detected only in B16-SIY, MC57-SIY and MCA-OVA cells. Exposure to IL-17A or IL-17Fin 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 alsoresponded to these cytokines by down-regulating these mediators, consistent with its higher IL17RDexpression, a subunit reported to inhibit IL-17/IL-17RA-RC signaling. Remarkably, noresponse to IL-17A/F was detected in EL4-SIY and C1498-SIY that may be associated to the lack ofIL-17RC expression. Finally, we evaluated tumor progression in IL-17-signaling-deficient incomparison to WT mice and determined that tumor volume was augmented at several days postinjectionof 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 resultshighlight that IL-17-signaling role in overall tumor progression may be influenced by particularprofiles 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 differenttumor types.