Study of the role of the cytokines of the IL-17 family in the CTL immunity against tumors

RODRIGUEZ C.; TOSELLO BOARI J.; ARAUJO FURLAN C.; CANALE F.; GRUPPI A.; MONTES C.L.; ACOSTA RODRIGUEZ E.V.

Buenos Aires

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Inmunología; 2015

Sociedad Argentina de Inmunología

We demonstrated that during T. cruzi infection, intrinsic IL-17RA signaling mediates survival and proper activation of specific CD8+ T cells (CTLs), preventing early exhaustion. Because highly-functional CTL are critical for host-resistance to cancer, we evaluated the role of IL-17/IL-17R in modulating tumor-specific CTL immunity and tumor progression. For this, we used the melanoma model induced by injection of OVA-expressing B16-cells in WT mice. By real-time PCR we detected the IL-17RA-encoding transcripts in B16-cells, tumor, draining (D) and non-draining (ND) lymph nodes (LN) and spleen. Moreover, IL-17RC transcript was detected in B16-cells and tumor and IL-17F was detected in B16-cells, tumor and DLN. In contrast, IL-17A, IL-17C, and IL-17RE transcripts were low/undetectable in all samples. Next, we evaluated the specific and total CTL responses and tumor progression in WT, IL-17RA-knockout (KO) and IL-17A/F-KO-mice. We determined that tumor-bearing IL-17RA-KO-mice showed reduced numbers of total and tumor-specific CD8+ T cells (p<0.05) and increased expression of several inhibitory receptors in comparison to WT counterparts. Furthermore, IL-17RA-KO-mice presented enhanced tumor progression evidenced by higher tumor weight (p=0.0021). Interestingly, IL-17A/F-KO-mice showed a similar phenotype than IL-17RA-KO-mice in terms of altered CTL responses but showed a tumor growth comparable to WT mice. Our results provide evidences that IL-17/IL-17R favors anti-tumor CTL immunity during cancer. This, together with the reported effect of IL-17 cytokines in survival and proliferation of tumor cells, highlights that the IL-17/IL-17R axis has several opposite effects in tumor growth. This should be considered when designing therapies aimed at targeting this cytokine family in cancer.