2. Academic Validation
  3. Cytokine-like molecule CCDC134 contributes to CD8⁺ T-cell effector functions in cancer immunotherapy

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

  • Cancer Res. 2014 Oct 15;74(20):5734-45. doi: 10.1158/0008-5472.CAN-13-3132.
Jing Huang 1,  Lin Xiao 2,  Xiaoting Gong 1,  Wenwei Shao 1,  Yanhui Yin 3,  Qinyuan Liao 1,  Yang Meng 3,  Yingmei Zhang 1,  Dalong Ma 1,  Xiaoyan Qiu 4
Affiliations

Affiliations

  • 1 Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China. Peking University Center for Human Disease Genomics, Beijing, China.
  • 2 Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China. Department of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Peking University Center for Human Disease Genomics, Beijing, China.
  • 3 Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
  • 4 Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China. Peking University Center for Human Disease Genomics, Beijing, China. [email protected].
PMID: 25125657 DOI: 10.1158/0008-5472.CAN-13-3132
Abstract

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.

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