Cytokine-like molecule CCDC134 contributes to CD8+ T Cell effector functions in cancer immunotherapy

CCDC134 is a poorly characterized secreted protein that may act as an immune cytokine. Here we show that CCDC134 is differentially expressed on resting and activated immune cells and that it promotes CD8+ T cell activation, proliferation and cytotoxicity by augmenting expression of the T cell effector molecules IFN-γ, TNF-α, granzyme B and perforin. CCDC134 facilitated infiltration of CD8+ T cells with enhanced cytolytic activity into tumors, demonstrating strong antitumor effects in a CD8+ T cell-dependent manner. Mechanistically, in CD8+ T cells exposure to CCDC134 promoted cell proliferation through the JAK3-STAT5 pathway, a classic feature of many cytokines of the common γ-chain (γc) cytokine receptor family. Overall, our results provide evidence that CCDC134 may serve as a member of the γc cytokine family, and they show illustrate its potent antitumor effects by augmenting CD8+ T cell-mediated immunity.