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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.
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1 Seoul National University College of Medicine, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
2 Seoul National University College of Medicine, Department of Interdisciplinary Program in Cancer Biology, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
3 Seoul National University Hospital, Seoul National University College of Medicine, Department of Pathology, Seoul, Republic of Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X)
4 Seoul National University Bundang Hospital, Department of Pathology, Seongnam, Korea (GRID:grid.412480.b) (ISNI:0000 0004 0647 3378)
5 Seoul National University Hospital, Seoul National University College of Medicine, Department of Surgery, Seoul, Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X)
6 Seoul National University Hospital, Seoul National University College of Medicine, Department of Surgery, Seoul, Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X); Seoul National University College of Medicine, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
7 Seoul National University Hospital, Seoul National University College of Medicine, Department of Pathology, Seoul, Republic of Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X); Seoul National University College of Medicine, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)