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

Abstract

Aims The protein expression of programmed death‐ligand 1 (PD‐L1) has been recognised as being a biomarker for poor prognosis in diffuse large B‐cell lymphoma (DLBCL). The aims of this study were to determine PD‐L1 DNA status and mRNA status, and to explore whether they contribute to protein expression and their clinicopathological correlation in DLBCL. Methods and results In this study, we used fluorescence in‐situ hybridisation, RNA in‐situ hybridisation and immunohistochemistry to determine PD‐L1 status at three different levels in 287 DLBCL samples with follow‐up. Their correlation and clinical pathological relevance were also analysed. Our results showed that 1.7% (3/175) of patients had PD‐L1 DNA amplification, 19.9% (57/287) had high PD‐L1 mRNA expression, and 11.8% (34/287) had high PD‐L1 protein expression. Both mRNA and protein expression of PD‐L1 were significantly higher in non‐germinal centre B‐cell‐like (GCB) DLBCL than in GCB DLBCL (P < 0.05). In addition, the patients with high PD‐L1 mRNA or high PD‐L1 protein expression but no PD‐L1 DNA amplification had significantly poorer overall survival (OS) than those with low PD‐L1 expression (P < 0.05). Furthermore, we found that PD‐L1 mRNA and PD‐L1 protein expression were highly correlated (P = 0.012), which was observed in all three samples with DNA amplification. Conclusions PD‐L1 DNA amplification is a rare event, PD‐L1 mRNA is the main contributor to the high PD‐L1 protein expression, and the latter two will serve as important biomarkers for predicting the prognosis of DLBCL patients and selecting them for immunotherapy.

Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death‐ligand 1 (PD‐L1) axis in post‐transplant lymphoproliferative disorders: association with Epstein–Barr virus, PD‐L1 copy number alterations, and outcome

“…PD‐L1 CNAs have not been thoroughly studied in PTLD. In our study, PD‐L1 CNAs were frequently found in DLBCL cases in variable percentages of cells, as opposed to the low frequency of PD‐L1 CNAs reported in DLBCL cases in the non‐immunodeficiency setting . Therefore, our findings confirm that PD‐L1 CNAs and PD‐L1 up‐regulation are common in immunodeficiency states such as PTLD …”

“…We demonstrated that PD‐L1 expression was associated with the non‐GCB subtype, as reported in DLBCL in immunocompetent individuals . Furthermore, PD‐L1 expression was associated with clinical features such as the presence of B symptoms and high levels of β2m, probably reflecting a highly proinflammatory tumour microenvironment.…”

“…Thirty‐seven cases showed high FISH detection quality, according to previously described criteria, including 25 DLBCL cases, eight polymorphic PTLD cases, and the four CHL cases. Overall, 11 (30%) cases were classified as disomic, five (13%) as polysomic, 12 (32%) as having copy gains, and nine (24%) as amplified (Figures and ).…”

Epstein–Barr virus-positive diffuse large B-cell lymphoma features disrupted antigen capture/presentation and hijacked T-cell suppression

“…A high frequency of PD-L1/PD-L2-involving genetic aberrations was observed in EBV-positive diffuse large B-cell lymphoma (DLBCL, 19%) 19 However, one study by another group from our department shows that PD-L1 genetic alteration is a rare event even in the EBV+ positive subgroup. 25 In our EBV+ positive cohort, no PD-L1 genetic alteration was identified either.…”

Comparison of PD‐L1 detection assays and corresponding significance in evaluation of diffuse large B‐cell lymphoma

“…This might be caused by the limited number of cases and the scoring method for the RNAscope assay, which was continuous and subjective. Sun et al also used RNAscope method to evaluate PD‐L1 mRNA expression in DLBCL, and the cutoff used was different from our study. We tried the cutoff reported and other possible cutoff value, but none of them showed prognostic value.…”