Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22 Zhongguancun South Avenue, Beijing, 100081, People's Republic of China.
National Center of Stomatology & National Clinical Research Center for Oral Diseases, Beijing, 100081, People's Republic of China.
Funct Integr Genomics. 2023 May 10;23(2):155. doi: 10.1007/s10142-023-01082-4.
Adenoid cystic carcinoma (ACC) is one of the most common malignancy of the major salivary glands with a high recurrence rate and poor prognosis. Determining tumor heterogeneity and factors in the microenvironment may provide novel therapeutic targets for ACC. We performed single-cell RNA sequencing of one ACC sample and normal salivary gland tissues from a patient to analyze tumor heterogeneity, immunosuppressive landscape, and intercellular communication networks. The heterogeneity of epithelial cells in ACC tissues was significantly higher compared with that in normal tissues, whereas immune cells were almost absent. We found four malignant cell clusters in ACC and explored their characteristics and function. In tumor tissues, CD8 + cytotoxic T cells and CD4 + T helper cells were significantly decreased, whereas IgA + plasma cells were absent. There were two clusters of macrophages, one representing IL1B macrophages and the other consisted of a cluster of macrophages associated with the epithelial mesenchymal transition (EMT). Both were significantly different from the normal tissue composition. In addition, the communication between epithelial cells and other cells in the tumor tissue was enhanced. MIF-CD74 and APP-CD74 were significantly upregulated. We comprehensively described the heterogeneity of ACC and the tumor microenvironment (TME) from a single cell perspective including cell characteristics, immune cell infiltration, and cell communication. CLINICAL RELEVANCE: This study provided further insights into ACC and may lead to new treatment strategies.
腺样囊性癌（ACC）是大涎腺癌中最常见的恶性肿瘤之一，具有高复发率和预后不良的特点。确定肿瘤异质性和微环境中的因素可能为 ACC 提供新的治疗靶点。我们对一名 ACC 患者的一个样本和正常涎腺组织进行了单细胞 RNA 测序，以分析肿瘤异质性、免疫抑制景观和细胞间通讯网络。与正常组织相比，ACC 组织上皮细胞的异质性显著更高，而免疫细胞几乎不存在。我们在 ACC 中发现了四个恶性细胞簇，并探索了它们的特征和功能。在肿瘤组织中，CD8+细胞毒性 T 细胞和 CD4+辅助性 T 细胞显著减少，而 IgA+浆细胞不存在。有两种巨噬细胞簇，一种代表 IL1B 巨噬细胞，另一种由与上皮间质转化（EMT）相关的巨噬细胞簇组成。两者与正常组织组成均有显著差异。此外，肿瘤组织中上皮细胞与其他细胞之间的通讯增强。MIF-CD74 和 APP-CD74 显著上调。我们从单细胞角度全面描述了 ACC 和肿瘤微环境（TME）的异质性，包括细胞特征、免疫细胞浸润和细胞通讯。临床相关性：这项研究进一步深入了解了 ACC，并可能为新的治疗策略提供依据。
