title: Cytokine-like molecule CCDC134 contributes to CD8⁺ T-cell effector functions in cancer immunotherapy.
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.
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Gong
authors.affiliation: 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.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.affiliation: 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. qiuxy@bjmu.edu.cn.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005260:Female; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008565:Membrane Proteins / Q000494:pharmacology / Q000502:physiology*; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C576232:CCDC134 protein, human; D008565:Membrane Proteins; D007371:Interferon-gamma