Expression of the immune checkpoint molecules PD‑L1 and PD‑1 in EBV‑associated lymphoproliferative disorders: A meta‑analysis

Abstract

Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders. In this process, the role of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) has remained to be clarified. A meta-analysis of 20 studies was performed and risk ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the association between PD-L1/PD-1 expression and the status of EBV infection. The results showed that the expression level of PD-L1 in tumor cells was significantly higher in EBV(+) cases with a pooled RR of 2.26 (95% CI, 1.63-3.14; P<0.01), particularly in subtypes of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma. Similarly, EBV infection increased the expression of PD-L1 in immune cells with a pooled RR of 2.20 (95% CI, 1.55-3.12; P<0.01). In subtypes of DLBCL and post-transplant lymphoproliferative disorder, the expression of PD-L1 in immune cells is increased in EBV(+) cases. Regarding the expression level of PD-1 in tumor-infiltrating lymphocytes (TILs), no significance was found between EBV infection and PD-1 expression, with a pooled RR of 1.10 (95% CI, 0.81-1.48; P>0.05). The present meta-analysis demonstrated that in EBV-associated lymphoproliferative disorders, EBV infection was associated with the expression level of PD-L1 in tumor cells and immune cells but was not associated with the expression of PD-1 in TILs.