Selective blockade of B7‐H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma |
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| Authors: | Liang Mao Teng‐Fei Fan Lei Wu Guang‐Tao Yu Wei‐Wei Deng Lei Chen Lin‐Lin Bu Si‐Rui Ma Bing Liu Yansong Bian Ashok B Kulkarni Wen‐Feng Zhang Zhi‐Jun Sun |
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| Institution: | 1. The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, China;2. Department of Oral Maxillofacial‐Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China;3. Gastrointestinal Oncology Section, Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;4. Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA |
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| Abstract: | Immature myeloid cells including myeloid‐derived suppressor cells (MDSCs) and tumour‐associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7‐H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using immunocompetent transgenic HNSCC models, we observed that targeting inhibition of B7‐H3 reduced tumour size. Flow cytometry analysis revealed that targeting inhibition of B7‐H3 increases antitumour immune response by decreasing immunosuppressive cells and promoting cytotoxic T cell activation in both tumour microenvironment and macroenvironment. Our study provides direct in vivo evidence for a rationale for B7‐H3 blockade as a future therapeutic strategy to treat patients with HNSCC. |
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| Keywords: | B7‐H3
HNSCC
immunotherapy myeloid‐derived suppressor cells tumour‐associated macrophages |
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