Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma

Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address...

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Published in:Cell death & disease 2024-01, Vol.15 (1), p.15-15, Article 15
Main Authors: Chen, Jierong, Huang, Qunsheng, Li, Yi-Qi, Li, Zhi, Zheng, Jiabin, Hu, Weixian, Yang, Yuesheng, Wu, Deqing, Bei, Jin-Xin, Gu, Bing, Wang, Junjiang, Li, Yong
Format: Article
Language:English
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13/51
631/67/1504/1829
631/67/2329
Adenocarcinoma
Adenocarcinoma - genetics
Antibodies
Biochemistry
Biomedical and Life Sciences
Cancer
Cancer-Associated Fibroblasts
Cell Biology
Cell Culture
Cell interactions
Esophageal cancer
Esophagogastric Junction
Gastric cancer
Humans
Immunology
Life Sciences
Lymphocytes T
Single-Cell Analysis
Stomach Neoplasms - genetics
T cell receptors
Therapeutic targets
Tumor Microenvironment
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Summary:Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-023-06388-6