PD-L1 Expression Associated with Epstein—Barr Virus Status and Patients’ Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil

Abstract

Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein–Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan–Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.

Epstein–Barr Virus Infection in Cancer

“…De Fátima Aquino Moreira-Nunes, C. et al [ 9 ] assessed the correlation between EBV status, PD-L1 expression, and overall survival among GC patients. This study revealed that EBV-positive GC presented a high relative expression of PD-L1 and that the high expression of PD-L1 increases the overall survival of GC patients.…”

Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment

“…Of note, gene expression signatures associated with viral infection were predictive of better overall survival in HNSCC and bladder cancer ( 147 ), and high T cell infiltration was predictive of overall survival in HPV + HNSCC but not in HPV - samples ( 148 ). In gastric cancer, EBV + tumors also had increased expression of immune checkpoints ( 149 ) and IRF3 gene signature ( 150 ). Using single-cell transcriptomics, it has recently been shown that malignant cells from EBV + gastric cancers were distinguished by a gene expression signature composed of IFN-I-activated and antigen-presenting molecules ( 151 ).…”