The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma

Xia, Fang; Xu, Bing; Yang, Zhi-Zhang; Qiu, Weiliu; Zhang, Long; Zhang, Suxia; Wu, Yunjin; Zhu, Xuyou; Chen, Xue; Xie, Shuanshuan; Yi, Xianghua; Liang, Aibin; Zeng, Yu

doi:10.1097/md.0000000000006398

Cited by 54 publications

(74 citation statements)

References 36 publications

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“…PD‐L1 protein and mRNA expression levels were significantly related to COO with higher PD‐L1 expression in patients with non‐GC type LBCL compared with patients with GCB type. This finding is a reproduction of results from three previous studies . However, as explained above, our study cohort was enriched by MYC and DH patients, which applies a selection bias, and, therefore, the cohort may not be fit to investigate the distribution of COO.…”

Section: Discussionsupporting

confidence: 64%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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. [8][9][10][11][12] Treatments targeting the PD-L1/PD-1 pathway has been successfully introduced in treatment of Hodgkin lymphoma and some solid cancers, 4,5,7 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, 7 it may do the same in LBCL.…”

Section: Discussionmentioning

confidence: 99%

“…8 PD-L1 expression in DLBCL has been investigated in a few studies. [9][10][11][12] Expression of PD-L1 in tumour cells seems to predict response to therapy with PD-L1/PD-1 inhibitors in Hodgkin lymphoma, 7 and further studies will elucidate whether it can be used as a predictive marker in DLBCL as well. PD-L1 expression in MYC-driven DLBCL has been investigated in one study, 9 whereas no reports have been published on PD-L1 expression in DH lymphomas.…”

Section: Introductionmentioning

confidence: 99%

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

Elbæk

Pedersen

Breinholt

et al. 2019

Hematological Oncology

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In large B‐cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD‐L1/PD‐1 pathway are still poorly elucidated in LBCL. PD‐L1 expression might predict response to treatment targeting the PD‐L1/PD‐1 pathway. We therefore investigated the relationship between PD‐L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD‐L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD‐L1 mRNA expression by next‐generation RNA sequencing (NGS) in another 77 patients. Twenty‐four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD‐L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0‐10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0‐10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3‐30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5‐30.0), P = .004 and P ≤ .001, respectively. PD‐L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD‐L1 protein and mRNA expression levels were associated with non–germinal centre (GC) type compared with germinal centre B‐cell (GCB)‐type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD‐L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD‐L1/PD‐1‐inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Elbæk

Pedersen

Breinholt

et al. 2019

Hematological Oncology

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“…In this study, we found that four cases (44.4%) were PD‐L1‐positive. Expression of PD‐L1 in DLBCL has been previously reported and is associated with overall poor prognosis . IVLBCL in general has a poor outcome, except for the cases limited only to the skin .…”

Section: Discussionmentioning

confidence: 93%

A study of PD‐L1 expression in intravascular large B cell lymphoma: correlation with clinical and pathological features

2019

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Intravascular large B cell lymphoma (IVLBCL) is a rare, aggressive, extranodal large B cell lymphoma characterised by growth of tumour cells within the lumen of vessels, particularly capillaries. Programmed cell death ligand 1 (PD‐L1) is a cell surface glycoprotein that interacts with programmed death 1 (PD‐1) on the T cell surface, leading to modulation of the immune response. PD‐L1 is a targetable immune check‐point molecule that is expressed on neoplastic cells in various cancers, including a subset of lymphomas. We correlated the expression of PD‐L1 with clinical and pathological findings in this rare disease. Eleven cases of IVLBCL were identified in the archives of Laboratory of Pathology at the National Cancer Institute, NIH. A panel of immunostains (CD20, CD3, CD5, PD‐L1) was performed. The cases were classified as the classic form or the variant associated with haemophagocytic syndrome (HPS) based on published 2017 WHO criteria. Three cases (27.3%) were HPS variant and eight cases (72.7%) were the classic form. Five (45.5%) of 11 cases were CD5‐positive; two of three (66%) were HPS variants and three of eight (37.5%) were classic form. Overall, four of nine evaluable cases (44.4%) were positive for PD‐L1, three of which were classic. Only one CD5‐positive case was PD‐L1‐positive, a classic variant. In summary, a subset of IVLBCL express PD‐L1. Although limited, these data suggest that PD‐L1 is expressed in both the so‐called classic form as well as the HPS variant. PD‐L1 is expressed irrespective of CD5 expression. Finally, detection of PD‐L1 expression in a subset of IVLBCL lymphoma cases may identify patients who might benefit from targeted immunotherapy.

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Expression and prognostic significance of the PD‐1/PD‐L1 pathway in AIDS‐related non‐Hodgkin lymphoma

Zhao,

Cai,

Xiao

et al. 2024

Cancer Medicine

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ObjectiveImmune tolerance and evasion play a critical role in virus‐driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD‐1) and its ligands, PD‐L1 and PD‐L2, in aggressive acquired immunodeficiency syndrome (AIDS)‐related non‐Hodgkin lymphoma (AR‐NHL) remain poorly understood, particularly in the Epstein–Barr virus (EBV)‐positive subset.MethodsWe used in situ hybridization with EBV‐encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD‐1/PD‐L1/L2 pathway in a multi‐institutional cohort of 58 patients with AR‐NHL and compared EBV‐positive and EBV‐negative cases.ResultsThe prevalence of EBV+ in AR‐NHL was 56.9% and was associated with a marked increase in the expression of PD‐1/PD‐L1/PD‐L2 in malignant cells. Patients with AR‐NHLs who tested positive for both EBER and PD‐1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD‐L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD‐1 tissue‐expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD‐1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD‐L1 (r = 0.354, p = 0.014) expression.ConclusionsThese data emphasize the importance of PD‐1‐mediated immune evasion in the complex landscape of immune oncology in AR‐NHL co‐infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup.

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The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma

Abstract: Supplemental Digital Content is available in the text

Cited by 54 publications

References 36 publications

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

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

A study of PD‐L1 expression in intravascular large B cell lymphoma: correlation with clinical and pathological features

Expression and prognostic significance of the PD‐1/PD‐L1 pathway in AIDS‐related non‐Hodgkin lymphoma

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