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

Abstract 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.