Association Between Intra-Tumoral Immune Response and Programmed Death Ligand 1 (PD-L1) in Gastric Cancer

BACKGROUND: Targeting of PD-1/PD-L1 immune checkpoints exhibits excellent clinical outcomes in numerous types of solid tumors, including gastric cancer. However, the tumor microenvironment of gastric cancer is very complex and the association of PD-L1 with the tumor microenvironment in gastric cancer is still not clear. MATERIAL/METHODS: This study analyzed the characteristics of PD-L1 expression and used immunohistochemistry to assess CD8 and CD4 tumor-infiltrating leucocytes (TILs) in 478 cases of gastric cancer compared with the expression patterns in 70 matched adjacent tissues, and 32 cases of benign gastric tissues. Standardized methods for TILs assessment in gastric cancer were used. RESULTS: The results indicated that PD-L1 expression was increased in gastric cancer tissues (193 out of 478, 40.37%) compared with matched adjacent tissues (14 out of 70, 20.00%) and benign gastric tissues (10 out of 32, 31.25%). It was observed that in gastric cancer patients, positive PD-L1 status in tumor cells (tPD-L1) was associated with distant metastasis (χ(2)=3.344, P=0.044). The positive expression pattern of tPD-L1 was associated with higher density of TILs, and this pattern was most significant in the non-metastasis group, compared to the metastasis group. We also found that tPD-L1 was not prognostic for overall survival in gastric cancer patients, but tPD-L1 and tCD8 combined positive status in gastric cancer patients was strongly associated with better overall survival rates both in the univariate analysis [hazard ratio (HR)=2.341, 95% confidence interval (CI)=1.147–3.556, P<0.001 and in the multivariate analysis (HR=1.844, 95% CI=1.136–2.592, P=0.031). CONCLUSIONS: These data suggested an interaction between tPD-L1 expression and TILs in gastric cancer, and tPD-L1 expression positively correlated with high densities of tCD8 and indicated a better overall survival and decreased metastasis in gastric cancer patients.