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- Title
High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8<sup>+</sup> T cells in dMMR/MSI-H gastric cancer.
- Authors
Kanoda, Ryo; Nakajima, Shotaro; Fukai, Satoshi; Saito, Motonobu; Saito, Katsuharu; Suzuki, Hiroya; Kikuchi, Tomohiro; Nirei, Azuma; Okayama, Hirokazu; Mimura, Kosaku; Hanayama, Hiroyuki; Sakamoto, Wataru; Momma, Tomoyuki; Saze, Zenichiro; Kono, Koji
- Abstract
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.
- Subjects
STOMACH cancer; T cells; DNA mismatch repair; TUMOR-infiltrating immune cells; TUMOR microenvironment; TUMORS; INTERFERONS
- Publication
Scientific Reports, 2024, Vol 14, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-024-71974-3