Endogenous ICOS signaling supports Th17 therapy efficacy

Abstract Objective: We sought to determine the mechanism by which antigen-specific Th17 cells are able to clear melanoma tumors more effectively than their Th1 counterparts and to expand on the role of ICOS in the success of Th17 therapy. Methods: Antigen-specific TRP-1 CD4+ T cells were polarized to Th17 or Th1 phenotypes and were adoptively transferred into mice bearing B16F10 melanoma. The role of inducible costimulatory molecule (ICOS) in this therapy response was evaluated by antibody blockade and genetic deletion. RNA-Sequencing, flow cytometry, and tumor growth measurements were additionally used to assess differences when ICOS was blocked or not. Summary of Results: ICOS is important for the efficacy of Th17 therapy in mice with established melanoma as when blocking ICOS signaling via antibody or genetic means, both antitumor activity and survival was diminished. By assessing the phenotype of both infused and host lymphocytes, we found that B cell proliferation and the engraftment of transferred cells decreased in the mice blocked of ICOS signaling. I also found that ICOS signaling appears to be important early on after Th17 cells infusion, as blocking ICOS at early but not later time points compromised antitumor immunity. Conclusions: ICOS is important for long-term survival and antitumor activity of mice treated with Th17 cells targeting melanoma.