Interleukin-17 signaling influences CD8+ T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells

RODRIGUEZ, CONSTANZA; ARAUJO FURLAN, CINTIA L.; TOSELLO BOARI, JIMENA; BOSSIO, SABRINA N.; BOCCARDO, SANTIAGO; FOZZATTI, LAURA; CANALE, FERNANDO P.; BECCARIA, CRISTIAN G.; NUÑEZ, NICOLÁS G.; CESCHIN, DANILO G.; PIAGGIO, ELIANE; GRUPPI, ADRIANA; MONTES, CAROLINA L.; ACOSTA RODRÍGUEZ, EVA V.

OncoImmunology

Taylor and Francis Ltd.

Año: 2023 vol. 12

2162-4011

IL-17 immune responses in cancer are controversial, with both tumor-promoting and tumor-repressing effects observed. To clarify the role of IL-17 signaling in cancer progression, we used syngeneic tumor models from different tissue origins. We found that deficiencies in host IL-17RA or IL-17A/F expression had varying effects on the in vivo growth of different solid tumors including melanoma, sarcoma, lymphoma, and leukemia. In each tumor type, the absence of IL-17 led to changes in the expression of mediators associated with inflammation and metastasis in the tumor microenvironment. Furthermore, IL-17 signaling deficiencies in the hosts resulted in decreased anti-tumor CD8+ T cell immunity and caused tumor-specific changes in several lymphoid cell populations. Our findings were associated with distinct patterns of IL-17A/F cytokine and receptor subunit expression in the injected tumor cell lines. These patterns affected tumor cell responsiveness to IL-17 and downstream intracellular signaling, leading to divergent effects on cancer progression. Additionally, we identified IL-17RC as a critical determinant of the IL-17-mediated response in tumor cells and a potential biomarker for IL-17 signaling effects in tumor progression. Our study offers insight into the molecular mechanisms underlying IL-17 activities in cancer and lays the groundwork for developing personalized immunotherapies.