Predictive relevance of PD-L1 expression with pre-existing TILs in gastric cancer

Abstract

Expression of programmed cell death receptor ligand 1 (PD-L1) has been shown to be up-regulated in some gastric cancer patients and to correlate with the density of tumour infiltrating lymphocytes (TILs). However, conflicting results have been reported regarding TILs and the expression of PD-L1 as a prognostic marker for gastric cancer. We investigated the correlation of PD-L1 and TILs expression with clinicpathological characteristics in 105 well characterized gastric cancer patients. PD-L1 expression and CD3+ and CD8+ TILs were evaluated by fluorescent multiplex immunohistochemistry (mIHC) analysis. PD-L1 positive staining on tumour cells was observed in 35% cases and 48% cases showed PD-L1 expression on immune cells. Up-regulated PD-L1 expression on tumour cells and immune cells was associated with high density of pre-existing tumour infiltrating CD3+ and CD8+. In additional, more than 70% tumor infiltrating CD3+ cells were CD3+CD8+ cells. More than 60% PD-L1+ immune cells were PD-L1+CD3+CD8+ cells. PD-L1 expression in tumour cells was associated with poor prognosis and high density CD3+ and CD8+ TILs indicated improved overall survival in gastric cancer patients. Increased PD-L1 expression with low density CD3+ and CD8+ TILs had the shortest overall survival. In accordingly, PD-L1 absence with high density CD3+ and CD8+ TILs indicated the best prognosis. Combination of PD-L1 with pre-existing TILs may be more precise than PD-L1 alone for predicting survival in gastric cancer.