Wu Lei, Yu Guang-Tao, Deng Wei-Wei, Mao Liang, Yang Lei-Lei, Ma Si-Rui, Bu Lin-Lin, Kulkarni Ashok B, Zhang Wen-Feng, Zhang Lu, Sun Zhi-Jun
The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan, Hubei, China.
Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University,Wuhan, Hubei, China.
Oncoimmunology. 2018 Mar 13;7(4):e1397248. doi: 10.1080/2162402X.2017.1397248. eCollection 2018.
Head and neck squamous cell carcinoma (HNSCC) is considered as an immunosuppressive disease, with impaired tumor-infiltrating T lymphocytes and increased suppressive immune cells. The efficacy of CD47 antibodies in immune checkpoint therapy is not clearly understood in HNSCC. In this study, human tissue microarrays and immunocompetent transgenic mouse models were used to explore the expression of CD47 and the use of CD47 antibodies in HNSCC. We identified overexpression of CD47 in HNSCC as compared with the control normal human tissue and also in HNSCC mouse models. The expression of CD47 also correlated with clinicopathological parameters as well as outcome. Furthermore, inhibition of CD47 delayed tumor growth and improved tumor microenvironment by stimulating effector T cells and decreasing suppressive immune cells and regulating the function of CD11b Ly6G MDSC. Our data suggest that CD47 blockade may be a potential immunotherapeutic target in human HNSCC.
头颈部鳞状细胞癌(HNSCC)被认为是一种免疫抑制性疾病,其肿瘤浸润性T淋巴细胞功能受损,抑制性免疫细胞增多。在HNSCC中,CD47抗体在免疫检查点治疗中的疗效尚不清楚。在本研究中,使用人体组织微阵列和具有免疫活性的转基因小鼠模型来探究HNSCC中CD47的表达及CD47抗体的应用。我们发现,与对照正常人体组织相比,HNSCC中CD47过表达,在HNSCC小鼠模型中亦是如此。CD47的表达还与临床病理参数及预后相关。此外,抑制CD47可通过刺激效应T细胞、减少抑制性免疫细胞及调节CD11b Ly6G MDSC的功能来延缓肿瘤生长并改善肿瘤微环境。我们的数据表明,阻断CD47可能是人类HNSCC潜在的免疫治疗靶点。