单位：[1]Department of Immunology, U.T. MD Anderson CancerCenter, 7455 Fannin St., Houston, TX 77054, USA[2]Department of Melanoma, U.T. MD Anderson CancerCenter, 7455 Fannin St., Houston, TX 77054, USA[3]Departments of Lymphoma and Myeloma, U.T. MD Anderson CancerCenter, 7455 Fannin St., Houston, TX 77054, USA[4]Center for Inflammation and Epigenetics, Houston Methodist Research Institute,6670 Bertner Ave, Houston, TX 77030, USA[5]Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA[6]Department of Pathology andImmunology, Baylor College of Medicine, Houston, TX 77030, USA[7]Institute for Immunology and School of Medicine, TsinghuaUniversity, Beijing, 100084, China[8]The Campbell Family Institute for Breast Cancer Research at Princess Margaret CancerCentre, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada[9]Department of Microbiologyand Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA[10]The Second Xiangya Hospital,Central South University, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center forMetabolic Diseases, 139 Renmin Road, Changsha, Hunan 410011, China[11]EMD Serono Research and Development Institute, Inc.45A Middlesex Turnpike, Billerica, MA 01821, USA[12]Center for Cancer and Immunology Research, Children’s National HealthSystem, Washington DC, 20010 USA[13]Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, 100029,China[14]X-KANG United Biopharmaceutical Science & Technology Co. Ltd., Suzhou, Jiangsu 215000, China[15]Department ofCancer Biology Betsy B. DeWindt Endowed Chair for Cancer Research, Lerner Research Institute, Cleveland Clinic, 9500 EuclidAvenue, Cleveland, OH 44195, USA[16]City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity. Expression of B7-H3 was found in multiple tumor lines, tumor-infiltrating dendritic cells, and macrophages. B7-H3-deficient mice or mice treated with an antagonistic antibody to B7-H3 showed reduced growth of multiple tumors, which depended on NK and CD8(+) T cells. With a putative receptor expressed by cytotoxic lymphocytes, B7-H3 inhibited their activation, and its deficiency resulted in increased cytotoxic lymphocyte function in tumor-bearing mice. Combining blockades of B7-H3 and PD-1 resulted in further enhanced therapeutic control of late-stage tumors. Taken together, our results indicate that the B7-H3 checkpoint may serve as a novel target for immunotherapy against cancer.
基金：
Beijing Municipal Science and Technology [Z171100000417005]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81502462]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016672] Funding Source: NIH RePORTER
第一作者单位：[1]Department of Immunology, U.T. MD Anderson CancerCenter, 7455 Fannin St., Houston, TX 77054, USA
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推荐引用方式(GB/T 7714)：
Young-hee Lee,Natalia Martin-Orozco,Peilin Zheng,et al.Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function[J].CELL RESEARCH.2017,27(8):1034-1045.doi:10.1038/cr.2017.90.
APA：
Young-hee Lee,Natalia Martin-Orozco,Peilin Zheng,Jing Li,Peng Zhang...&Chen Dong.(2017).Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function.CELL RESEARCH,27,(8)
MLA：
Young-hee Lee,et al."Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function".CELL RESEARCH 27..8(2017):1034-1045
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