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High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR/MSI-H gastric cancer
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High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR/MSI-H gastric cancer
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High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR/MSI-H gastric cancer
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Journal Article
High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR/MSI-H gastric cancer
2024
Overview
Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits an immune-active tumor microenvironment (TME) compared to MMR proficient (pMMR)/microsatellite stable/Epstein-Barr virus-negative [EBV (−)] GC. The tumor cell-intrinsic cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway has been considered a key regulator of immune cell activation in the TME. However, its significance in regulating the immune-active TME in dMMR/MSI-H GC remains unclear. Here, we demonstrated that tumor cell-intrinsic cGAS–STING was highly expressed in dMMR GC compared to pMMR/EBV (−) GC. The expression of tumor cell-intrinsic STING was significantly and positively associated with the number of CD8
+
tumor-infiltrating lymphocytes in GC. Analysis of TCGA datasets revealed that the expression of interferon-stimulated genes and STING downstream T-cell attracting chemokines was significantly higher in MSI-H GC compared to other subtypes of GC with EBV (−). These results suggest that tumor cell-intrinsic STING signaling plays a key role in activating immune cells in the dMMR/MSI-H GC TME and might serve as a novel biomarker predicting the efficacy of immunotherapy for GC treatment.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Aged
/ CD8+ tumor-infiltrating lymphocytes
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Cyclic GMP–AMP synthase–stimulator of interferon genes
/ DNA Mismatch Repair - genetics
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Lymphocytes, Tumor-Infiltrating - immunology
/ Lymphocytes, Tumor-Infiltrating - metabolism
/ Male
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Nucleotidyltransferases - genetics
/ Nucleotidyltransferases - metabolism
/ Science
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - immunology
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - pathology
/ Tumor Microenvironment - immunology
/ Tumor-infiltrating lymphocytes
/ Tumors
