Programmed cell death-ligand 1 (PD-L1) + tumour cells and low-reacting programmed cell death 1 (PD1) + tumour-infiltrating lymphocytes predict poor prognosis in Epstein–Barr virus + diffuse large B-cell lymphoma

Epstein–Barr virus (EBV) + diffuse large B-cell lymphoma (DLBCL) has specific tumour cell characteristics, and these patients have worse outcomes than EBV-negative DLBCL patients. We compared 38 EBV + DLBCL patients with 43 methotrexate-associated EBV + B-cell lymphoproliferative disorders (MTX + /EBV + BLPDs) and 30 non-germinal centre (GC) subtype DLBCL. Lymphoma cells of the EBV + DLBCL group were positive for BCL2 in 17 patients (44.7%), CMYC in 23 patients (60.5%), and p53 in 33 patients (86.8%), which was significantly higher than in the MTX + /EBV + BLPD group ( P < 0.05), and were positive for CD30 in 29 patients (76.3%), compared with two in non-GC subtype DLBCL (6.7%) ( P < 0.0001). Significantly more EBV + DLBCL patients ( n = 16, 42.1%) had programmed cell death-ligand 1 (PD-L1) + tumour cells than patients with non-GC subtype DLBCL ( n = 5, 16.7%; P = 0.024), and PD-L1 + tumour cells were more common in advanced stages than in early stages ( P = 0.048). Twenty-five EBV + DLBCL patients (69.4%) had few reactive PD1 + tumour-infiltrating lymphocytes (TILs), compared with 12 patients with MTX + /EBV + BLPDs (37.5%) ( P = 0.008). In the EBV + DLBCL group, CD30, BCL2, CMYC, and p53 expression was not related to patient prognosis. Poor outcomes were associated with PD-L1 + tumour cells ( P = 0.001) and low-reacting PD1 + TILs ( P = 0.02), while their combination conferred a worse outcome ( P < 0.0001). Immune evasion by PD-L1 + tumour cells and exhaustion of PD1 + TILs may occur in EBV + DLBCL patients, and PD-L1/PD1 interactions may influence tumour progression and poor prognosis.