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The tumor cell-intrinsic cyclic GMP\u2013AMP synthase (cGAS)\u2013stimulator 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\u2013STING was highly expressed in dMMR GC compared to pMMR\/EBV (\u2212) GC. The expression of tumor cell-intrinsic STING was significantly and positively associated with the number of CD8<jats:sup>+<\/jats:sup> 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 (\u2212). 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.<\/jats:p>","DOI":"10.1038\/s41598-024-71974-3","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T15:02:21Z","timestamp":1725634941000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR\/MSI-H gastric cancer"],"prefix":"10.1038","volume":"14","author":[{"given":"Ryo","family":"Kanoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Fukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motonobu","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuharu","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azuma","family":"Nirei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Okayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosaku","family":"Mimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Hanayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Momma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenichiro","family":"Saze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"71974_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/S0140-6736(20)31288-5","volume":"396","author":"EC Smyth","year":"2020","unstructured":"Smyth, E. 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