Gastric Microbiome Alterations Are Associated with Decreased CD8+ Tissue-Resident Memory T Cells in the Tumor Microenvironment of Gastric Cancer.

Cancer Immunol Res

Department of General Surgery, Research Center for Clinical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

Published: October 2022

AI Article Synopsis

  • The study examines the relationship between gastric microbiota and gastric cancer progression, focusing on how changes in microbiota may relate to immune system dysfunction.
  • Using advanced sequencing techniques, researchers analyzed the microbiota from tumor tissues of 53 gastric cancer patients and 30 chronic gastritis patients.
  • Key findings reveal that the presence of the Methylobacterium genus is linked to lower immune activity and worse patient outcomes, indicating its potential role in influencing tumor behavior and progression in gastric cancer.

Article Abstract

The host microbiota is closely associated with tumor initiation and progression in multiple solid tumors including gastric cancer. The aim of this study was to investigate in patients with gastric cancer whether there are alterations in gastric microbiota and any potential association these may have with immune dysregulation. 16S rRNA gene sequencing was used to analyze tumor microbiota of 53 patients with gastric cancer and gastric mucosal tissue microbiota of 30 patients with chronic gastritis. The effect of microbiota on the tumor microenvironment (TME) was studied by single-cell sequencing, immunohistochemistry, multiplex immunofluorescence staining, and flow cytometry, as well as in a mouse model of primary gastric cancer. The gastric cancer microbiota was characterized by reduced microbial diversity and enrichment of the Oceanobacter, Methylobacterium, and Syntrophomonas genera. Intratumoral Methylobacterium was significantly associated with poor prognoses in patients with gastric cancer. It also was inversely correlated with the frequency of CD8+ tissue-resident memory T (TRM) cells in the TME. TGFβ was significantly reduced in gastric cancer samples with higher abundance of Methylobacterium. Finally, we verified that Methylobacterium can decrease TGFβ expression and CD8+ TRM cells in the tumor by establishing a mouse model of primary gastric cancer. The results suggest that tumor microbiota and exhausted CD8+ TRM cells in the TME of gastric cancer are significantly correlated, and that Methylobacterium may play a role in gastric carcinogenesis.

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Source
http://dx.doi.org/10.1158/2326-6066.CIR-22-0107DOI Listing

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