Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+T Cell Density
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(2021)
摘要
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/mm(2) in tumour centre vs. 414.9/mm(2) in invasive front) when compared to B7-H3-low group (157.7/mm(2) vs. 218.7/mm(2), 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.
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关键词
B7-H3,CD8-Positive T-Lymphocytes,gastric cancer,immune checkpoint,immune evasion,immunohistochemistry,tumour escape,tumour microenvironment
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