Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density

Int J Mol Sci. 2021 Feb 21;22(4):2129. doi: 10.3390/ijms22042129.

Abstract

CD8+ T cells are the main effector cells of anti-cancer immune response that can be regulated by various costimulatory and coinhibitory molecules, including members of the B7 family. B7 homolog 3 (B7-H3) appears as a promising marker for immunotherapy; however, its significance in gastric cancer (GC) is unclear yet. We evaluated the spatial distribution of CD8+ T cells in relation to the expression of B7-H3 by double immunohistochemical staining. The level of B7-H3 intensity was scored manually (0-3) and dichotomized into B7-H3-low and B7-H3-high groups. The distribution and density of CD8+ T cells was analysed using whole slide digital imaging. B7-H3 was expressed mainly in the stromal compartment of GC (n = 73, 76% of all cases). Tumours with high expression of B7-H3 showed larger spatial differences of CD8+ T cells (86.4/mm2 in tumour centre vs. 414.9/mm2 in invasive front) when compared to B7-H3-low group (157.7/mm2 vs. 218.7/mm2, respectively) (p < 0.001). This study provides insight into the expression pattern of B7-H3 in GC of Western origin. In GCs with higher level of B7-H3 expression, CD8+ T cells were spatially suppressed in the tumour centre suggesting that B7-H3 might be involved in tumour escape mechanisms from the immune response.

Keywords: B7-H3; CD8-Positive T-Lymphocytes; gastric cancer; immune checkpoint; immune evasion; immunohistochemistry; tumour escape; tumour microenvironment.

MeSH terms

  • Aged
  • B7 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Lymphocyte Count
  • Male
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology*
  • Stromal Cells / metabolism
  • Survival Analysis

Substances

  • B7 Antigens
  • CD276 protein, human