Abstract
BackgroundThe programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.MethodsWe reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical (IHC) assay. The expression of anaplastic lymphoma kinase (ALK), CD5, CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein–Barr virus (EBV)-encoded RNAs (EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan–Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.ResultsOf the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype (P = 0.02 and P = 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment (P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression (r = − 0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival (OS) rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells (P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS (P < 0.01).ConclusionsPD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.
Highlights
The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses
The inclusion criteria were as follows: (1) patients with newly diagnosed Diffuse large B-cell lymphoma (DLBCL) treated at the Sun Yat-sen University Cancer Center between October 2005 and August 2012; (2) patients were diagnosed using biopsy according to the 2001 or 2008 World Health Organization classification; (3) patients were 18 years of age or older; (4) patients had received first-line chemotherapy regimens, such as R-CHOP or R-CHOP-like regimen, CHOP or CHOPlike regimen, and MA regimen with curative intent; (5) patients were not infected with human immunodeficiency virus and were not with immunodeficiency disease or second tumor; and (6) complete clinical information was available, including follow-up data
In the present study, we investigated the expression of Programmed cell death-ligand 1 (PD-L1) in tumor cells and in tumor microenvironment in DLBCL patients
Summary
The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Binding of PD-L1 to its receptor, programmed cell death 1 (PD-1), inhibits cytokine production and cell cycle progression of T cells [3,4,5]. It functions as an important checkpoint in the regulation of cellular and humoral immune responses [6]. Previous studies have reported that PD-L1 is involved in the negative regulation of immune responses by binding to the PD-1 receptor and results in cancer cells evading the host immune surveillance and the promotion of metastasis [9]
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