Infiltration And Significance Of CD103~+CD8~+T Cells In Gastric Cancer

Objective To investigate the degree of infiltration and distribution of tissue-resident CD8+T cells(CD103+CD8+T cells)in gastric cancer tissues,and to analyze the relationship between the degree of infiltration and clinicopathological features and prognosis.Methods Immunofluorescence staining was used to examine the CD103+CD8+ T cells infiltration in 90 cases of gastric cancer and their adjacent normal tissues included in a tissue microarray.Wilcoxon rank test was used to compare the CD8+T cells,CD103+CD8+T cells infiltration and CD103+CD8+T cells/CD8+T cells ratio in gastric cancer and corresponding normal tissues.The chi-square test was used to analyze the relationship between CD8+T cells,CD103+CD8+T cells infiltration and CD103+CD8+T cells/CD8+T cells ratio in gastric cancer tissues and patient clinicopathological features.Kaplan-Meier survival analysis was performed to explore the correlation between CD8+T cells,CD 103+CD8+T cells infiltration and CD 103+CD8+T cells/CD8+T cells ratio and patient overall survival,Cox model was used to analyze the correlation between different clinical parameters and prognosis.Results There were no significant differences between the infiltration of CD8+T cells,CD103+CD8+T cells infiltration and CD103+CD8+T cells/CD8+T cells ratio in gastric cancer tissues and that in adjacent normal tissues(P>0.05).The infiltration rate of CD8+T cells in stage Ⅲ-Ⅳ cases(25.45%,14/55)was significantly lower than that in stage Ⅰ-Ⅱcases(45.71%,16/35)(x2=3.951,P=0.047).There was no significant correlation between CD8+T cells infiltration and other clinicopathological features(P>0.05).The infiltration rate of CD103+CD8+T cells in stage Ⅲ-Ⅳ cases(69.09%,38/55)was significantly lower than that in stage Ⅰ～Ⅱ cases(91.43%,32/35)(χ~2=6.175,P=0.013).There was no significant correlation between CD103+CD8+T cells infiltration and other clinicopathological features(P>0.05).The infiltration rate of CD103+CD8+T cells/CD8+T cells in stage Ⅲ～Ⅳ cases(70.91%,39/55)was significantly lower than that in stage Ⅰ～Ⅱ cases(88.57%,31/35)(χ~2=3.860,P=0.049).There was no significant correlation between CD103+CD8+T cells/CD8+T cells ratio and other clinicopathological features(P>0.05).Kaplan-Meier survival analysis showed that patients with high CD8+T cells infiltration showed significantly longer overall survival(OS)than patients with low CD8+T cells infiltration(HR=1.959,95%CI:1.115～3.441,P=0.0139).Multivariate Cox model analysis indicated that tumor diameter(HR=1.940,95%CI:1.111～3.389,P=0.020)and CD8+T cells high infiltration(HR=0.486,95%CI:0.258-0.917,P=0.026)were independent prognostic factors for gastric cancer.The OS of patients with high CD103+CD8+T cells infiltration was significantly longer than that of patients with low CD103+CD8+T cells infiltration(HR=2.187,95%CI:1.062～4.500,P=0.0336).Multivariate Cox model analysis indicated that tumor diameter(HR=2.031,95%CI:1.163～3.546,P=0.013)and high CD103+CD8+T cells infiltration(HR=0.516,95%CI:0.285v0.934,P=0.029)were independent prognostic factors for gastric cancer.The OS of patients with high CD103+CD8+T cells/CD8+T cells ratio was significantly longer than that of patients with low CD103+CD8+T cells/CD8+T cells ratio(HR=2.157,95%CI:1.051v4.425,P=0.0361).Multivariate Cox model analysis indicated that tumor diameter(HR=2.149 95%CI:1.230～3.752,P=0.007)and CD103+CD8+ cells/CD8+T cells ratio(HR=0.396,95%CI:0.207～0.758,P=0.005)were independent prognostic factors for gastric cancer.Flow cytometry-assisted detection demonstrated high infiltration of CD103+CD8+T cells in gastric cancer tissues,which were effectively cytotoxic.Conclusion CD103+CD8+T cells are associated with good prognosis in gastric cancer tissues,suggesting that they play an important role in the inhibition of gastric carcinogenesis and development,and can be used as an important factor in the prognosis evaluation of gastric cancer patients.