PD-1 expression on tumour-infiltrating cells is a prognostic factor for relapsed or refractory diffuse large B-cell lymphoma

Background: The tumour microenvironment (TME), which is modulated after immune-chemotherapy, is involved in tumour growth and metastasis. Programmed cell death 1 (PD-1) expressed on tumour-infiltrating non-malignant cells plays an important role in the TME through the PD-1/programmed cell death ligand 1 (PD-L1) signalling pathway. However, its impact in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains unclear.Methods: We conducted a retrospective study using tissue samples at relapse for patients with R/R DLBCL (n = 45) and evaluated the clinical impact of PD-1 expression on tumour-infiltrating non-malignant cells (microenvironmental PD-1, mPD-1). In addition, corresponding 27 samples at diagnosis were analysed to evaluate the changes in PD-1/PD-L1 expression in the TME after chemotherapy.Results: Patients with mPD-1(+) DLBCL showed significantly better overall survival compared with patients with mPD-1(-) DLBCL (hazard ratio, 0.30, p = 0.03). Among patients with mPD-1(-) DLBCL, those positive for neoplastic or microenvironmental PD-L1 (nPD-L1(+) or mPD-L1(+)) showed significantly worse outcomes. Microenvironmental PD-1 and PD-L1 expression has high correlation at relapse, although none was found at diagnosis.Conclusion: We determined the clinical impact of microenvironmental PD-1 expression and its relationship with neoplastic or microenvironmental expression of PD-L1 in patients with R/R DLBCL. The expression of PD-1 and PD-L1 in the TME dramatically changes during the chemotherapy. Therefore, evaluating TME at relapse, not at diagnosis is useful to predict the outcomes of R/R DLBCL patients.