Deficiency in the IL-17RA/IL-17 pathway affects primary and secondary antitumor responses promoting tumor growth

C RODRIGUEZ; J TOSELLO BOARI; C ARAUJO FURLAN; FP CANALE; CG BECCARIA; A GRUPPI; CL MONTES; EV ACOSTA RODRIGUEZ

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2016

The role of IL-17 cytokines in cancer remains controversial as both anti- and pro-tumoral effects have been described. We and others demonstrated that IL-17family plays a central role for the induction of NK and CD8+ T cell (CTL) responses. As these subsets are critical for host resistance to cancer, we evaluated the role of IL-17/IL-17R in modulating anti-tumor immunity and tumor progression. To this end, B6 (WT), IL-17RA KO (RKO) and IL-17A/F double KO (DKO) mice were injected with tumor cell lines that displayed progressor (B16-OVA, B16-SIY and MCA101-OVA) and regressor (MC57-SIY) growth patterns. Tumor progression and immune responses were studied at different days (d) post-injection (pi). Upon injection of B16 cells, RKO and DKO mice showed increased tumor volume and weight in comparison to WT mice (p<0.05, d21pi). In contrast,tumors induced by MCA101 cells had similar volumes in DKO and WT mice. Although RKO and DKO rejected MC57 tumors as efficient as WT mice, they presented higher tumor volumes between d3-8pi (p<0.05). Initial studies showed that MC57-bearing DKO mice presented at d12pi reduced numbers of SIY-specific CTL in draining-lymph nodes in comparison to WT controls (p<0.05). In addition, SIY-specific CTL from DKO mice displayed decreased frequency of cells with memory phenotype (CD62L+CD127+). As the memory CTL response developed in WT mice upon MC57-SIY cell injection is critical to protect hosts against challenge with B16-SIY tumors, we evaluated whether the SIY-specific CTL elicited in immunized RKO and DKO mice were also efficient against challenge. Of note, while all immunizedWT never develop tumor or were tumor-free at d20pi of B16-SIY cells, 100% of the immunized DKO and RKO mice developed tumors and only 50% were tumor-freeat d20 post-challenge. Altogether, our results indicate that the IL-17/IL-17RA pathway likely modulate primary and secondary CTL responses against tumors and may have a protective role during certain types of cancers.