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. [ABSTRACT FROM AUTHOR]