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 IFNγ, TNFα, 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 (γ(c)) cytokine receptor family. Overall, our results provide evidence that CCDC134 may serve as a member of the γ(c) cytokine family and illustrate its potent antitumor effects by augmenting CD8(+) T-cell-mediated immunity.