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

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.