Prognostic significance of CD8 and TCF1 double positive T cell subset in microsatellite unstable gastric cancer

Sci Rep. 2024 Nov 21;14(1):28810. doi: 10.1038/s41598-024-80450-x.

Abstract

Microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits high tumor-infiltrating lymphocyte (TIL) density. Despite the recognized significance of the immune microenvironment in MSI-H GC, our understanding of TIL remains limited. This study aimed to investigate the clinicopathologic and prognostic implications of T cell subsets in MSI-H GC. Single immunohistochemistry (IHC) for CD8, TCF1, and CD103, and double IHC for CD8/TCF1 and CD8/CD103 were performed in 382 surgically resected MSI-H GC samples. Densities of single or double positive immune cells were quantified and correlated with clinicopathologic features and overall survival (OS). TCF1 + cell densities showed weak correlations with CD8 + and CD103 + cell densities, while CD8+/TCF1 + cell density moderately correlated with CD8+/CD103 + cell density (R2 = 0.539, p < 0.001). Single IHC analyses showed no significant associations between CD8+, TCF1+, or CD103 + cell densities and OS (p > 0.05). Notably, elevated CD8+/TCF1 + cell density and a high CD8+/TCF1 + to CD8 + ratio correlated with less aggressive clinicopathologic features and improved OS (p = 0.017 and 0.001, respectively). Multivariable Cox-regression identified CD8+/TCF1 + to CD8 + ratio as an independent prognostic factor (p = 0.028). We demonstrated the prognostic significance of CD8+/TCF1 + to CD8 + ratio using double IHC in a large cohort of MSI-H GC.

Keywords: Alpha E integrins; Microsatellite instability; Stomach neoplasms; T cell transcription factor 1; Tumor-Infiltrating Lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • Female
  • Hepatocyte Nuclear Factor 1-alpha* / genetics
  • Hepatocyte Nuclear Factor 1-alpha* / metabolism
  • Humans
  • Immunohistochemistry
  • Integrin alpha Chains
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / immunology
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • HNF1A protein, human
  • alpha E integrins
  • Antigens, CD
  • Integrin alpha Chains