The prognostic significance of programmed cell death protein 1 and its ligand on lymphoma cells and tumor-immune cells in diffuse large B-cell lymphoma, not otherwise specified

• Published in: Radiology and oncology 2024-03, Vol.58 (1), p.99-109
• Main Authors: Slak, Teja Cas, Miceska, Simona, Gasljevic, Gorana, Boltezar, Lucka, Kloboves-Prevodnik, Veronika
• Format: Article
• Language: English
• Subjects: Apoptosis; B-cell lymphoma; B7-H1 Antigen - metabolism; Cell death; Clinical outcomes; diffuse large B-cell lymphoma; Gene expression; Germinal centers; Humans; Immune checkpoint inhibitors; Immune response; Immune system; Immunohistochemistry; Immunotherapy; Ligands; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - pathology; Movement disorders; Non-Hodgkin's lymphoma; Patients; PAX5; Pax5 protein; PD-1; PD-1 protein; PD-L1; PD-L1 protein; Prognosis; Programmed Cell Death 1 Receptor - therapeutic use; Proteins; Staining; Survival; Survival analysis; Targeted cancer therapy; Tumors
• ISSN: 1581-3207; 1318-2099; 1581-3207; 0485-893X
• DOI: 10.2478/raon-2024-0010

Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type non-Hodgkin's lymphoma, where the treatment of relapsed/refractory cases is the major challenge. Programmed cell death protein 1 (PD-1) and its ligand PD-L1 play a crucial role in the negative regulation of the immune response against the disease. The aim of the study was to analyze the expression of PD-1 and PD-L1 on lymphoma cells (LCs) and tumor-immune cells (TICs) and to investigate their correlation with outcome. Samples from 283 patients diagnosed with DLBCL, NOS (both germinal center B cell like [GCB] and non-GCB subtypes) were included in the study. Expression of PD-1 and PD-L1 was determined using double immunohistochemical staining (D-IHC) for PD-1/PAX5 and PD-L1/PAX5 on tissue microarrays. LCs were highlighted by D-IHC to obtain more accurate results. Clinical data and histologic diagnoses were obtained from electronic data records. We correlated clinical characteristics, and PD-1 and PD-L1 expression on LCs and TICs with progression-free survival (PFS) and overall survival (OS). Expression of PD-1 on TICs was observed in 38.4% and on LCs in 8.8% of cases, while PD-L1 was expressed on TICs in 46.8% and on LCs in 6.5% of cases. PD-L1 expression on LCs was more frequent in non-GCB subtype (p = 0.047). In addition, patients with PD-L1 expression on LCs had significantly shorter PFS (p = 0.015), and the expression retained significant in the multivariate model (p = 0.034). PD-L1 was more frequently expressed in LCs of the non-GCB subtype. Additionally, PD-L1 in LCs may predict shorter PFS time. D-IHC staining for PD-L1/PAX5 is a feasible method to assess PD-L1 expression on LCs of DLBCL, NOS patients and can be used to identify patients who may benefit from targeted immunotherapy with checkpoint inhibitors.