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Single‐Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Esophageal Squamous Cell Carcinoma
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Single‐Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Esophageal Squamous Cell Carcinoma
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Journal Article
Single‐Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Esophageal Squamous Cell Carcinoma
2023
Overview
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 inhibiting tumor growth and overcoming metastasis to improve clinical outcomes. Here not only a high‐resolution landscape of the tumor, immune, and stromal compartments is provided in metastatic lymph node but also metastatic‐specific patterns comparing with primary tumor are highlighted, which provide insights that may help to shape the tumor microenvironment and inform the development of new strategies against these prometastatic nontumor components for inhibiting tumor growth and overcoming metastasis.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Carcinoma, Squamous Cell - metabolism
/ Cells
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - metabolism
/ esophageal squamous carcinoma
/ Esophageal Squamous Cell Carcinoma - genetics
/ Genomes
/ Genomics
/ Humans
/ immunofluorescence and immunohistochemistry
/ lymph node metastatic microenvironment
/ Patients
/ Tumor Microenvironment - genetics
/ Tumors
