Clinicopathological and Immunomicroenvironment Characteristics of Epstein–Barr Virus-Associated Gastric Cancer in a Chinese Population

BACKGROUND: Epstein–Barr virus-associated gastric cancer(EBVaGC)has a unique tumor immune microenvironment. We performed a comprehensive analysis of the tumor-infiltrating immune cells in a cohort of EBVaGC in a Chinese population. METHODS: Epstein–Barr encoding region (EBER) in situ hybridization was performed in 1,328 consecutive cases of surgically resected GC. Densities of immune cells, including T cells, B cells, natural killer cells, and macrophages from the patients were calculated after immunohistochemical staining with CD3, CD20, CD57, and CD68 antibodies in tissue microarrays, respectively. RESULTS: EBVaGC patients accounted for 4.1% (55 of 1,328) cases in the overall population. The average age of patients with EBVaGC was lower than that of non-EBVaGC patients. Histologically, EBVaGC patients exhibited poorly differentiated adenocarcinoma (P = 0.004) and lower frequency of vascular invasion (P = 0.034). The density of CD3(+) T lymphocytes (CD3, 23.84 ± 14.49 vs. 12.76 ± 8.93, P < 0.001) and CD68(+) macrophages (CD68, 9.73 ± 5.25 vs. 5.44 ± 4.18, P < 0.001) was significantly higher in EBVaGC patients. CD3(+) T cell density predicted better 5-year overall survival of EBVaGC patients (P = 0.022). CONCLUSIONS: EBVaGC patients were younger with low-differentiated adenocarcinoma and less vascular invasion. Increased infiltration of multiple immune cells affected the prognosis of patients, especially EBVaGC patients with more CD3(+) T lymphocytes, who survived longer.