title: Tumor Therapeutics Work as Stress Inducers to Enhance Tumor Sensitivity to Natural Killer (NK) Cell Cytolysis by Up-regulating NKp30 Ligand B7-H6.
abstract: Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin, 5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy (TNF-α), could up-regulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future.
authors.affiliation: From the Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Guoshuai
authors.initials: G
authors.lastname: Cao
authors.affiliation: From the Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China, ustcwj@mail.ustc.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: From the Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: From the Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.affiliation: From the Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: From the Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China, and sunr@ustc.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
mesh_terms: D060887:B7 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress; D015854:Up-Regulation
chemical_list: D060887:B7 Antigens; D008024:Ligands; C431710:NCR3 protein, human; C542363:NCR3LG1 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3
keywords: immunotherapy; natural killer cells (NK cells); stress; tumor immunology; tumor therapy