Deficiency in the IL-17RA/IL-17 pathway affects protective CD8+ T cell immunity in a model of tumor vaccination

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

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

The role of IL-17 cytokines in cancer remains controversial as anti- and pro-tumoral effects have been described. We and others demonstrated that IL-17 family plays a central role for the induction of NK and CD8+ T cell (CTL) responses. As these subsets are critical for cancer resistance, 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 exhibiting progressor (B16- SIY and MCA101-OVA) and regressor (MC57-SIY) growth patterns. Previously, we showed that volumes of B16 and MC57, but not MCA101, tumors were increased in RKO and DKO mice compared to WT mice at several days post injection (dpi). Analysis of the primary immune response against MC57 demonstrated that compared to WT controls, DKO mice presented reduced numbers of SIY-specific CTL in draining-lymph nodes at d12pi (p<0.05). Also, tumor-specific CTL displayed decreased frequency of cells with memory phenotype (CD62L+CD127+). As the memory CTL response developed in MC57-SIY-immunized WT mice is critical to host protection against challenge with B16-SIY tumors, we aimed at evaluating whether RKO and DKO mice were also able to generate protective SIY-specific CTL. Then, we challenged MC57-SIY immunized mice with B16-SIY tumor cells and determined tumor growth until day 32 post challenge (pc). While most (75%) of immunized WT mice rejected B16 tumor, DKO and RKO mice were less protected as only few mice (around 20%) were tumor free at d32pc (p<0.05). Accordingly, blood and tumors of DKO mice showed reduced frequency of SIY-specific CTL (p<0.05) as well as decreased tumor-specific cells with a memory effector phenotype (CD44+CD62L-; p<0.001) in comparison to WT controls at day 8pc. Altogether, our results suggest that the IL-17/IL-17RA pathway modulates primary and secondary antitumor CTL responses and may influence tumor progression in certain cancers.