DEFICIENCY IN THE IL-17RA/IL-17 PATHWAY AFFECTS PRIMARY AND SECONDARY ANTITUMOR RESPONSES PROMOTING TUMOR GROWTH.

RODRIGUEZ, CONSTANZA; TOSELLO BOARI, JIMENA; ARAUJO FURLAN, CINTIA; CANALE, FERNANDO; BECCARIA, CRISTIAN G; GRUPPI, ADRIANA; MONTES, CAROLINA L.; ACOSTA RODRIGUEZ E V

Mar del Plata

Congreso; LXIV Reunión científica anual de la Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE; 2016

Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE.

(848) DEFICIENCY IN THE IL-17RA/IL-17 PATHWAY AFFECTS PRIMARY AND SECONDARYANTITUMOR RESPONSES PROMOTING TUMOR GROWTHCONSTANZA RODRÍGUEZ, JIMENA TOSELLO BOARI, CINTIA ARAUJO FURLAN, FERNANDO PABLO CANALE,CRISTIAN GABRIEL BECCARIA, ADRIANA GRUPPI, CAROLINA LUCÍA MONTES,EVA VIRGINIA ACOSTA RODRÍGUEZCentro de Investigaciones en Bioquímica Clínica e Inmunología. CIBICI-CONICET. Departamento de Bioquímica Clínica.Facultad de Ciencias Químicas. Universidad Nacional de Córdoba.The role of IL-17 cytokines in cancer remains controversialas both anti- and pro-tumoral effects havebeen described. We and others demonstrated that IL-17family plays a central role for the induction of NK andCD8+ T cell (CTL) responses. As these subsets arecritical for host resistance to cancer, we evaluated therole of IL-17/IL-17R in modulating anti-tumor immunityand tumor progression. To this end, B6 (WT), IL-17RAKO (RKO) and IL-17A/F double KO (DKO) mice wereinjected with tumor cell lines that displayed progressor(B16-OVA, B16-SIY and MCA101-OVA) and regressor(MC57-SIY) growth patterns. Tumor progression andimmune responses were studied at different days (d)post-injection (pi). Upon injection of B16 cells, RKO andDKO mice showed increased tumor volume and weightin comparison to WT mice (p<0.05, d21pi). In contrast,tumors induced by MCA101 cells had similar volumesin DKO and WT mice. Although RKO and DKO rejectedMC57 tumors as efficient as WT mice, they presentedhigher tumor volumes between d3-8pi (p<0.05). Initialstudies showed that MC57-bearing DKO mice presentedat d12pi reduced numbers of SIY-specific CTLin draining-lymph nodes in comparison to WT controls(p<0.05). In addition, SIY-specific CTL from DKO micedisplayed decreased frequency of cells with memoryphenotype (CD62L+CD127+). As the memory CTLresponse developed in WT mice upon MC57-SIY cellinjection is critical to protect hosts against challenge withB16-SIY tumors, we evaluated whether the SIY-specificCTL elicited in immunized RKO and DKO mice were alsoefficient against challenge. Of note, while all immunizedWT never develop tumor or were tumor-free at d20pi ofB16-SIY cells, 100% of the immunized DKO and RKOmice developed tumors and only 50% were tumor-freeat d20 post-challenge. Altogether, our results indicatethat the IL-17/IL-17RA pathway likely modulate primaryand secondary CTL responses against tumors and mayhave a protective role during certain types of cancers.