1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
2 Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
J Dent Res. 2018 Jul;97(7):787-794. doi: 10.1177/0022034518758604. Epub 2018 Feb 27.
Targeted therapy using monoclonal antibodies (mAbs) has emerged as a widely used form of immunotherapy in head and neck squamous cell carcinoma (HNSCC). Membrane-associated glycoprotein CD317 has been preferentially overexpressed by multiple myeloma cells, and its humanized mAb has been previously used in clinical trials. However, overexpression of CD317 in HNSCC and its correlation with tumor immunity is still uncertain. Here, the immunoreactivity of CD317 was detected in human HNSCC tissue microarrays, which contained 43 oral mucosa samples, 48 dysplasia samples, and 165 primary HNSCC. We found that CD317 expression was up-regulated in HNSCC tumor cells, and the CD317 expression level was independent of the histological grade, tumor size, and lymph node metastasis. Moreover, Kaplan-Meier survival curve analysis showed that patients with high expression of CD317 had a poor prognosis compared with patients with low expression. Furthermore, CD317 overexpression in HNSCC was correlated with immune checkpoint molecules PD-L1, B7-H3, and B7-H4 and tumor-associated macrophage markers (CD68 and CD163). We also observed that CD317 was overexpressed in immunocompetent mouse HNSCC tissue compared with normal tissue. Taken together, our findings demonstrate that CD317 overexpression indicates poor prognosis and is correlated with immune-related components in this patient cohort. CD317 may serve as a potential target for effective immunotherapy of HNSCC.
靶向治疗使用单克隆抗体（mAbs）已成为头颈部鳞状细胞癌（HNSCC）中广泛使用的免疫疗法形式。膜相关糖蛋白 CD317 已被多发性骨髓瘤细胞优先过表达，其人类化 mAb 已在临床试验中使用。然而，CD317 在 HNSCC 中的过表达及其与肿瘤免疫的相关性尚不确定。在这里，我们在包含 43 个口腔粘膜样本、48 个发育不良样本和 165 个原发性 HNSCC 的人类 HNSCC 组织微阵列中检测了 CD317 的免疫反应性。我们发现 CD317 在 HNSCC 肿瘤细胞中上调，并且 CD317 的表达水平与组织学分级、肿瘤大小和淋巴结转移无关。此外，Kaplan-Meier 生存曲线分析表明，与低表达的患者相比，CD317 高表达的患者预后较差。此外，CD317 在 HNSCC 中的过表达与免疫检查点分子 PD-L1、B7-H3 和 B7-H4 以及肿瘤相关巨噬细胞标志物（CD68 和 CD163）相关。我们还观察到 CD317 在免疫功能正常的小鼠 HNSCC 组织中比正常组织中过表达。总之，我们的研究结果表明，CD317 过表达表明预后不良，并与该患者队列中的免疫相关成分相关。CD317 可能成为 HNSCC 有效免疫治疗的潜在靶点。
