Expression of PD-1 in Tumor Cells is Associated with Shorter Survival in Non-metastatic Intestinal-type Gastric Adenocarcinoma.

Abstract

There is an urgent need to discover novel prognostic biomarkers and treatment strategies for gastric cancer (GC) patients. Several immune-related markers have been proposed as prognostic tools and immunotherapeutic targets to manage diseases. In this regard, we evaluated the expression pattern and prognostic significance of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), CD45RO+ tumor-infiltrating lymphocytes (TILs), and DNA mismatch repair (MMR) proteins (MLH1, MSH2, PMS2, and MSH6) in non-metastatic intestinal-type gastric adenocarcinoma. Samples and data from 70 GC patients were collected. Immunohistochemistry staining was used to detect the markers. We then evaluated the prognosis significance of each marker and their intercorrelation. Cytoplasmic PD-1 expressed by tumor cells was significantly associated with poorer survival. However, multivariate analysis indicated stronger prognostic values for TNM stage, tumor location, and extracellular mucin. A significant positive association was found between CD45ROhigh TILs and PD-1 expression on tumor-infiltrating cells (TICs). All GC patients with deficient MMR (d‑MMR) had a higher number of CD45RO+ TILs and were associated with PD-1+ TICs and PD‑L1+ tumor cells (TCs). However, the difference was not statistically significant. Despite the association of PD‑1 overexpression on TCs with shorter overall survival, histopathological factors, including tumor location, TNM stage, and extracellular mucin, remain the most decisive prognostic factors in non-metastatic intestinal-type gastric adenocarcinoma. Additionally, our data support a prognostic role for d-MMR and CD45RO, but not PD-1 and PD-L1 expression on TICs.