Ding Zhuang, He Yijia, Fu Yong, Zhu Nisha, Zhao Mengxiang, Song Yuxian, Huang Xiaofeng, Chen Sheng, Yang Yan, Zhang Caihong, Hu Qingang, Ni Yanhong, Ding Liang
Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Department of Oral Pathology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Front Oncol. 2021 Jun 15;11:687430. doi: 10.3389/fonc.2021.687430. eCollection 2021.
CD38 belongs to the ribosyl cyclase family and is expressed on various hematological cells and involved in immunosuppression and tumor promotion. Although targeting CD38 antibodies has been approved for treatment of multiple myeloma, the function of CD38 in solid tumor, oral squamous cell carcinoma (OSCC) , has not been investigated.
This retrospective study included 92 OSCC samples and analyzed the spatial distribution of CD38 by immunohistochemistry (IHC). The values of diagnosis and prognosis of CD38 were evaluated. Additionally, 53 OSCC preoperative peripheral blood samples were used to be analyzed by flow cytometry. Tumor Immune Estimation Resource (TIMER) and cBioPortal databases were used to study CD38 level in various tumors and its correlation with tumor immune microenvironment in head and neck squamous cell carcinoma (HNSCC).
CD38 ubiquitously presented in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs). Patients with highly expressed CD38 in TCs (CD38) had higher TNM stage and risk of lymph node metastasis. Upregulation of CD38 in FLCs (CD38) was significantly associated with poor WPOI. Escalated CD38 in TILs (CD38) led to higher Ki-67 level of tumor cells. Moreover, patients with enhanced CD38 were susceptible to postoperative metastasis occurrence, and those with highly expressed CD38 independently predicted shorter overall and disease-free survival. Strikingly, patients with highly expressed CD38, but not CD38 and CD38, had significantly lower CD3CD4 T cells and higher ratio of CD3CD16CD56NK cells. The imbalance of immune system is attributed to dysregulated immune checkpoint molecules (VISTA, PD-1, LAG-3, CTLA-4, TIGIT, GITR) as well as particular immune cell subsets, which were positively correlated with CD38 expression in HNSCC.
CD38 is a poor prognostic biomarker for OSCC patients and plays a vital role in governing immune microenvironment and circulating lymphocyte homeostasis. Co-expression between CD38 and immune checkpoint molecules provides new insight into immune checkpoint therapy.
CD38属于核糖基环化酶家族，在多种血液学细胞上表达，参与免疫抑制和肿瘤进展。尽管靶向CD38的抗体已被批准用于治疗多发性骨髓瘤，但CD38在实体瘤——口腔鳞状细胞癌（OSCC）中的功能尚未得到研究。
这项回顾性研究纳入了92例OSCC样本，通过免疫组织化学（IHC）分析CD38的空间分布。评估CD38的诊断和预后价值。此外，使用53例OSCC术前外周血样本进行流式细胞术分析。利用肿瘤免疫评估资源（TIMER）和cBioPortal数据库研究各种肿瘤中CD38水平及其与头颈部鳞状细胞癌（HNSCC）肿瘤免疫微环境的相关性。
CD38普遍存在于肿瘤细胞（TCs）、成纤维细胞样细胞（FLCs）和肿瘤浸润淋巴细胞（TILs）中。肿瘤细胞中CD38高表达（CD38）的患者具有更高的TNM分期和淋巴结转移风险。成纤维细胞样细胞中CD38上调（CD38）与较差的无进展生存期显著相关。肿瘤浸润淋巴细胞中CD38升高（CD38）导致肿瘤细胞的Ki-67水平升高。此外，CD38增强的患者术后易发生转移，CD38高表达的患者独立预测总体生存期和无病生存期较短。引人注目的是，CD38高表达的患者，而非CD38和CD38高表达的患者，具有显著更低的CD3CD4 T细胞和更高的CD3CD16CD56NK细胞比例。免疫系统的失衡归因于免疫检查点分子（VISTA、PD-1、LAG-3、CTLA-4、TIGIT、GITR）以及特定免疫细胞亚群的失调，它们与HNSCC中CD38的表达呈正相关。
CD38是OSCC患者预后不良的生物标志物，在调节免疫微环境和循环淋巴细胞稳态中起重要作用。CD38与免疫检查点分子之间的共表达为免疫检查点治疗提供了新的见解。
