Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Cell Prolif. 2022 Jun;55(6):e13249. doi: 10.1111/cpr.13249. Epub 2022 May 13.
Endometrial cancer (EC) is one of the most common gynecologic malignancies with increasing morbidity. Cell-cell and cell-matrix interactions within the tumour microenvironment (TME) exert a powerful influence over the progression of EC. Therefore, a comprehensive exploration of heterogeneity and intratumoral crosstalk is essential to elucidate the mechanisms driving EC progression and develop novel therapeutic approaches.
4 EC and 2 normal endometrium samples were applied for single-cell RNA sequencing (scRNA-seq) analysis. In addition, we also included the public database to explore the clinical benefits of the single cell analysis.
9 types of cells were identified with specific expression of maker genes. Both the malignant epithelial cells and cells comprising the immune microenvironment displayed a high degree of intertumoral heterogeneity. Notably, the proliferation T cells also showed an exhausted feature. Moreover, the malignant cells may induce an immunosuppressive microenvironment through TNF-ICOS pair. Cancer-associated fibroblasts (CAFs) were divided into four subsets with distinct characteristics and they maintained frequent communications with malignant cells which facilitating the progression of EC. We also found that the existence of vascular CAF (vCAF) may indicate a worse prognosis for EC patients through integrating TCGA database.
The TME of human EC remains highly heterogeneous. Out finding that malignant cells interact closely with immune cells and vCAFs identifies potential therapeutic targets.
子宫内膜癌（EC）是最常见的妇科恶性肿瘤之一，发病率呈上升趋势。肿瘤微环境（TME）中的细胞-细胞和细胞-基质相互作用对 EC 的进展产生了强大的影响。因此，全面探索异质性和肿瘤内串扰对于阐明驱动 EC 进展的机制并开发新的治疗方法至关重要。
对 4 例 EC 和 2 例正常子宫内膜样本进行单细胞 RNA 测序（scRNA-seq）分析。此外，我们还纳入了公共数据库，以探讨单细胞分析的临床获益。
鉴定出 9 种具有特定标记基因表达的细胞类型。恶性上皮细胞和组成免疫微环境的细胞均表现出高度的肿瘤间异质性。值得注意的是，增殖性 T 细胞也表现出耗竭特征。此外，恶性细胞可能通过 TNF-ICOS 对诱导免疫抑制微环境。癌症相关成纤维细胞（CAFs）分为具有不同特征的四个亚群，它们与恶性细胞保持频繁的通信，促进了 EC 的进展。我们还发现，通过整合 TCGA 数据库，血管 CAF（vCAF）的存在可能预示着 EC 患者的预后更差。
人 EC 的 TME 仍然高度异质。我们的发现表明恶性细胞与免疫细胞和 vCAF 密切相互作用，确定了潜在的治疗靶点。
