Association of intratumoral PD-L1 expression with survival of patients with Epstein-Barr virus-associated gastric cancer.

e15590 Background: The present study analyzed the expression of tumoral (t-) PD-L1/L2 and stromal (str-) PD-L1/L2, and their impacts on the survival of a relatively large group of Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). Methods: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. Immunohistochemistry of PD-L1 and PD-L2 was carried out and the intensity was scored as an intensity score 0 (no staining), 1 (weak intensity), 2 (intermediate intensity), and 3 (high intensity). The expression was also evaluated in tumor tissues and stromal immune cells and divided into two groups (2 and 3 were interpreted as a positive result). Results: Among the 120 patients, 57 patients (47.5%) and 66 patients (55.0%) were determined as t-PD-L1-positive and str-PD-L1 positive, while 23 patients (19.2%) and 41 patients (34.2%) were determined as t-PD-L2-positive and str-PD-L2 positive. In a univariate analysis, t-PD-L1-positive was significantly associated shorter disease-free survival (DFS, P = 0.032), yet not overall survival (P = 0.482). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, gender, WHO classification, and tumor-infiltrating lymphocytes, t-PD-L1 positivity was independently associated with poor DFS (Hazard ratio = 4.183, P = 0.044). Meanwhile, in the univariate analysis, t-PD-L2-positive and str-PD-L2-positive showed a better DFS trend than t-PD-L2-negative and str-PD-L2-negative, respectively (P = 0.071 and P = 0.092). However, t-PD-L2 and str-PD-L2 expressions showed no prognostic significance on DFS in the multivariate analysis. Conclusions: The level of t-PD-L1 expression represents a significant difference for DFS in patients with EBVaGC. The current findings support the concept that PD-L1 may be a prognostic parameter for predicting patient outcome and act as a therapeutic target in EBVaGC.