This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein-Barr virus-associated gastric cancer (EBVaGC).
After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with EBVaGC identified by EBV-encoded RNA in situ hybridization was retrospectively analyzed using immunohistochemistry (IHC). For each IHC marker, positivity was separately in intraepithelial tumor cells (iTu-) and immune cells in the tumor stroma area (str-).
Among 116 eligible patients, 57 (49.1%) and 66 patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive, respectively, while 23 (21.6%) and 45 patients (38.8%) were determined as iTu-PD-L2-positive and str-PD-L2-positive, respectively. iTu-PD-L1-positivity was found to be significantly associated with lymph node (LN) metastasis (p=0.012) and a poor disease-free survival (DFS)(P=0.032), yet not overall survival (p=0.482). Meanwhile, str-PD-L1-positivity was correlated with the density of iTu- and str-tumor-infiltrating lymphocytes (TILs)(P=0.003, P=0.004, respectively), yet not the patient outcomes. In contrast, str-PD-L2-positivity was related to a lower T category (P=0.003), absence of LN metastasis (P=0.032) and perineural invasion (P=0.028), and iTu- and str-TILs (P
iTu-PD-L1 expression can be used to predict a poor outcome in patients with EBVaGC, and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy.
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All authors have declared no conflicts of interest.