Expression and clinical value of programmed cell death-ligand 1 (PD-L1) in diffuse large B cell lymphoma: a retrospective study

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.

Integrative analysis of PD‐L1 DNA status, mRNA status and protein status, and their clinicopathological correlation, in diffuse large B‐cell lymphoma

“…In our study, we chose the PD‐L1 IHC 22C3 pharmDx antibody from Dako North America, which has been used in a clinical phase 1 trial (KEYNOTE‐001) for advanced NSCLC patients; ≥50% of PD‐L1 expression in tumour cells correlates with significantly improved efficacy of pembrolizumab. Our results were consistent with those of the previous study, and suggested that use of the PD‐L1 IHC 22C3 pharmDx antibody might be a promising strategy in clinical trials for DLBCL patients . Furthermore, the subjectivity of pathologists may affect PD‐L1 protein expression results.…”

“…Hu et al . regarded cases with at least 5% of lymphoma cells showing distinct membranous and/or cytoplasmic staining as PD‐L1‐positive (antibody from Cell Signaling Technology, Shanghai, China); the results showed that positive PD‐L1 expression (49.0%) was associated with the non‐GCB subtype, and these patients had significantly lower 5‐year OS and 5‐year progression‐free survival . Kiyasu et al .…”

PD‐L1 expression is low in large B‐cell lymphoma with MYC or double‐hit translocation

“…We investigated the relationship between PD‐L1 expression and MYC and DH translocation and found a negative association between PD‐L1 expression levels in tumour cells and the presence of MYC and DH translocation in patients with LBCL. We aimed at investigating this relationship in order to achieve more consistent results as studies on PD‐L1 expression in LBCL up until now are few and show inconsistent results . Treatments targeting the PD‐L1/PD‐1 pathway has been successfully introduced in treatment of Hodgkin lymphoma and some solid cancers, but results are sparse regarding the effect of treatment in LBCL, and as PD‐L1 expression in tumour cells seems to predict outcome to treatment in Hodgkin lymphoma, it may do the same in LBCL.…”

“…One study investigated the relationship between PD‐L1 protein expression and MYC protein expression, and it found that PD‐L1 expression level in the tumour microenvironment was negatively correlated with MYC protein expression in 109 patients with DLBCL. They found no correlation between PD‐L1 expression and MYC protein expression in either tumour cells or tumour microenvironment.…”

“…PD‐L1 expression in DLBCL has been investigated in a few studies . Expression of PD‐L1 in tumour cells seems to predict response to therapy with PD‐L1/PD‐1 inhibitors in Hodgkin lymphoma, and further studies will elucidate whether it can be used as a predictive marker in DLBCL as well.…”