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

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

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

The role of IL-17 cytokines in cancer remains controversial asanti- and pro-tumoral effects have been described. We and othersdemonstrated that IL-17 family plays a central role for the inductionof NK and CD8+ T cell (CTL) responses. As these subsets arecritical for cancer resistance, we evaluated the role of IL-17/IL-17Rin modulating anti-tumor immunity and tumor progression. To thisend, 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 notMCA101, tumors were increased in RKO and DKO mice comparedto WT mice at several days post injection (dpi). Analysis of the primaryimmune response against MC57 demonstrated that compared toWT controls, DKO mice presented reduced numbers of SIY-specificCTL in draining-lymph nodes at d12pi (p<0.05). Also, tumor-specificCTL displayed decreased frequency of cells with memory phenotype(CD62L+CD127+). As the memory CTL response developed inMC57-SIY-immunized WT mice is critical to host protection againstchallenge with B16-SIY tumors, we aimed at evaluating whetherRKO and DKO mice were also able to generate protective SIY-specificCTL. Then, we challenged MC57-SIY immunized mice withB16-SIY tumor cells and determined tumor growth until day 32 postchallenge (pc). While most (75%) of immunized WT mice rejectedB16 tumor, DKO and RKO mice were less protected as only fewmice (around 20%) were tumor free at d32pc (p<0.05). Accordingly,blood and tumors of DKO mice showed reduced frequency ofSIY-specific CTL (p<0.05) as well as decreased tumor-specific cellswith a memory effector phenotype (CD44+CD62L-; p<0.001) in comparisonto WT controls at day 8pc. Altogether, our results suggestthat the IL-17/IL-17RA pathway modulates primary and secondaryantitumor CTL responses and may influence tumor progression incertain cancers.