Single‐Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Esophageal Squamous Cell Carcinoma

作者：Yongxu Jia, Baifeng Zhang, Chunyang Zhang, Dora Lai‐Wan Kwong, Zhiwei Chang, Shanshan Li, Zehua Wang, Huiqiong Han, Jing Li, Yali Zhong, Xin Sui, Li Fu, Xin‐Yuan Guan, Yanru Qin · 发表于：Advanced Science · 年份：2023 · DOI：10.1002/advs.202204565 · 被引用次数：92 · 研究领域：Immune cells in cancer、Cancer Immunotherapy and Biomarkers、Esophageal Cancer Research and Treatment

Abstract Lymph node metastasis, the leading cause of mortality in esophageal squamous carcinoma (ESCC) with a highly complex tumor microenvironment, remains underexplored. Here, the transcriptomes of 85 263 single cells are analyzed from four ESCC patients with lymph node metastases. Strikingly, it is observed that the metastatic microenvironment undergoes the emergence or expansion of interferon induced IFIT3 + T, B cells, and immunosuppressive cells such as APOC1 + APOE + macrophages and myofibroblasts with highly expression of immunoglobulin genes ( IGKC ) and extracellular matrix component and matrix metallopeptidase genes. A poor‐prognostic epithelial‐immune dual expression program regulating immune effector processes, whose activity is significantly enhanced in metastatic malignant epithelial cells and enriched in CD74 + CXCR4 + and major histocompatibility complex (MHC) class II genes upregulated malignant epithelia cells is discovered. Comparing with primary tumor, differential intercellular communications of metastatic ESCC microenvironment are revealed and furtherly validated via multiplexed immunofluorescence and immunohistochemistry staining, which mainly rely on the crosstalk of APOC1 + APOE + macrophages with tumor and stromal cell. The data highlight potential molecular mechanisms that shape the lymph‐node metastatic microenvironment and may inform drug discovery and the development of new strategies to target these prometastatic nontumor components for inhibit...