[Expression of the cGAS-STING Pathway in dMMR/MSI-H in Colorectal Cancer]

Gan To Kagaku Ryoho. 2022 Oct;49(10):1130-1132.
[Article in Japanese]

Abstract

Deficient mismatch repair (dMMR)/microsatellite instability (MSI)-H colorectal cancer (CRC) has high immunogenicity. Although the cyclic GMP-AMP synthase( cGAS)-stimulator of interferon genes( STING) pathway activation has considerably contributed to the high number of CD8+ tumor-infiltrating lymphocytes (TILs), its role in dMMR/MSI-H CRC is largely unknown. In this study, we investigated the association between cGAS-STING expression and CD8+ TILs in CRC. Data analysis using the TCGA dataset CRC cohort showed that cGAS, STING, and CD8 gene expression levels were significantly higher in the MSI group. Immunohistochemistry examination of resected clinical CRC samples showed that cGAS-STING expression in tumor cells was high in the MSI CRC, and CD8+ TILs was also significantly infiltrated in the MSI group. Moreover, significant CD8+ TILs infiltration was observed in CRC with high cGAS and STING expression levels. The results suggest that dMMR/MSI -H CRC has maintained a high cGAS-STING expression, which may contribute to abundant CD8+ TILs.

Publication types

  • English Abstract

MeSH terms

  • Colorectal Neoplasms* / pathology
  • DNA Mismatch Repair
  • Humans
  • Interferons / genetics
  • Microsatellite Instability*
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism

Substances

  • Nucleotidyltransferases
  • Interferons