Expression of B7-H3 was found in multiple human and murine tumor types, and in tumor-infiltrating dendritic cells and macrophages. Knockout of B7-H3 or inhibition by antibodies reduced tumor growth in mice and was dependent on NK and CD8+ T cells. B7-H3 was found to directly inhibit the activation of NK cells in the tumor microenvironment and its deficiency improved their cytolytic function.
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.Cell Research advance online publication 7 July 2017; doi:10.1038/cr.2017.90.
Author Info: (1) Department of Immunology. (2) Department of Immunology. EMD Serono Research and Development Institute, Inc. 45A Middlesex Turnpike, Billerica, MA 01821, USA. (3) Center for Inf
Author Info: (1) Department of Immunology. (2) Department of Immunology. EMD Serono Research and Development Institute, Inc. 45A Middlesex Turnpike, Billerica, MA 01821, USA. (3) Center for Inflammation and Epigenetics, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA. Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA. The Second Xiangya Hospital, Central South University, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, 139 Renmin Road, Changsha, Hunan 410011, China. (4) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China. (5) Center for Cancer and Immunology Research, Children's National Health System, Washington DC, 20010 USA. (6) Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, 100029, China. (7) Department of Molecular and Cellular Biology. (8) Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. (9) Department of Immunology. (10) Department of Immunology. (11) Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA. The Second Xiangya Hospital, Central South University, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, 139 Renmin Road, Changsha, Hunan 410011, China. (12) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China. (13) X-KANG United Biopharmaceutical Science &Technology Co. Ltd., Suzhou, Jiangsu 215000, China. (14) Center for Cancer and Immunology Research, Children's National Health System, Washington DC, 20010 USA. (15) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China. (16) Department of Melanoma. (17) Department of Melanoma. (18) Departments of Lymphoma and Myeloma, U.T. MD Anderson Cancer Center, 7455 Fannin St., Houston, TX 77054, USA. Department of Cancer Biology Betsy B. DeWindt Endowed Chair for Cancer Research, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. (19) Departments of Lymphoma and Myeloma, U.T. MD Anderson Cancer Center, 7455 Fannin St., Houston, TX 77054, USA. City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA. (20) Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, 100029, China. (21) The Campbell Family Institute for Breast Cancer Research at Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada. (22) Department of Molecular and Cellular Biology. (23) Department of Melanoma. EMD Serono Research and Development Institute, Inc. 45A Middlesex Turnpike, Billerica, MA 01821, USA. (24) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China. (25) Center for Inflammation and Epigenetics, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA. Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA. (26) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China.
