Tumor-Associated Macrophage Infiltration and PD-L1 Expression in Gastric Cancer According to a Modified TCGA-Based Classification

PURPOSE: Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood. MATERIALS AND METHODS: We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein-Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared. RESULTS: A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P