Abstract
CD8+ tumor-infiltrating lymphocytes (TILs) play a major role in antitumor immunity. High endothelial venules (HEVs) are related to diverse immune cells in solid tumors. We analyzed CD8+ and Foxp3+ TILs in combination with HEVs to determine their prognostic role in advanced gastric cancer (AGC). We enrolled 157 patients with AGC in this study. The densities of CD8+ TILs and Foxp3+ TILs were calculated using immunohistochemical staining. HEVs were evaluated by MECA-79 expression. HEVs were identified in 60 (38.2%) cases and was significantly associated with an increased number of CD8+ TILs (p = 0.027) but not of Foxp3+ TILs (p = 0.455) and CD20+ TILs (p = 0.163). A high CD8+/HEV+ level was significantly associated with nodal metastasis (p = 0.048). In survival analysis, patients with high CD8+/HEV+ levels demonstrated the longest overall survival (OS) (p = 0.015). Furthermore, a high CD8+/HEV+ level was an independent prognostic factor in AGC (p = 0.011; hazard ratio (HR) = 0.435; 95% confidence interval (CI) = 0.245–0.837). HEVs were found to play an important role in antitumor immunity associated with CD8+ TILs in AGC. This analysis of HEVs and CD8+ TILs helps stratify patients with AGC and sheds light on tumor immunity.
Highlights
Gastric cancer (GC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide [1]
Previous studies have noted that a high density of High endothelial venules (HEVs) in breast cancer and melanoma is associated with a favorable prognosis, possibly due to increased tumor infiltrative lymphocytes (TILs) and their phenotypes [13,14]
We investigated HEVs and CD8+, Foxp3+, and CD20+ TILs, along with their correlation with the clinicopathologic features of Advanced gastric cancer (AGC), and we evaluated the prognostic role of a combined analysis of HEVs and CD8+, Foxp3+, and CD20+ TILs
Summary
Gastric cancer (GC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide [1]. Recent studies have focused on controlling antitumor immunity through the tumor microenvironment. HEVs are characterized by the expression of peripheral node addressin and high levels of 6-sulfo sialyl Lewis X ligands. They are identified by the HEV-specific antibody MECA-79, which mediates the adherence and transendothelial migration of lymphocytes along the HEV vessel wall [10,11]. Previous studies have noted that a high density of HEVs in breast cancer and melanoma is associated with a favorable prognosis, possibly due to increased TILs and their phenotypes [13,14]. There have not been any combined analyses of HEVs and TILs conducted for gastric cancer
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