<scp>CD</scp>274 (<scp>PD</scp>‐L1)/<scp>PDCD</scp>1 (<scp>PD</scp>‐1) expression in de novo and transformed diffuse large B‐cell lymphoma

Kwiecińska, Anna; Tsesmetzis, Nikolaos; Ghaderi, Mehran; Kis, Lóránd; Saft, Leonie; Rassidakis, George Z.

doi:10.1111/bjh.14432

Cited by 24 publications

(22 citation statements)

References 10 publications

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“…Clone MRQ-22 (Cell Marque) The number of PD-1 1 TILs positively correlated with PD-L1 expression levels on tumor cells and/or macrophages. 62 31…”

Section: Pd-l1 Expression and Clinical Roles In B-cell Lymphomasmentioning

confidence: 99%

“…The amount of PD-1 1 TILs positively correlated with PD-L1 expression in tumor cells and/or macrophages in a study of 126 DLBCL patients 58 and in ABC-DLBCL in a study of 253 DLBCL patients, 61 as well as in histiocytes (but not PD-L1 on tumor cells) in a study of 20 de novo and 11 transformed (from FL) DLBCL patients ( Table 2). 62 The presence of or a high amount of PD-1 1 TILs in DLBCL samples has been associated with favorable, unfavorable, or no prognostic effect in different studies (Table 1) [56][57][58][59]63 ; increased PD-1 levels (percentage expression) in the peripheral blood of DLBCL patients have been associated with poorer prognosis. 64,65 In contrast to FL and DLBCL, chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) tissues have low numbers of PD-1 1 TILs (mean, 13 cells per mm 2 ) 46 ; however, the mean expression intensity of PD-1 was higher in CLL/SLL than in reactive lymph node samples.…”

Section: Introductionmentioning

confidence: 99%

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PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

Xu-Monette

Zhou

Young

2018

Blood

349

306

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Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1 tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1 T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas.

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“…Clone MRQ-22 (Cell Marque) The number of PD-1 1 TILs positively correlated with PD-L1 expression levels on tumor cells and/or macrophages. 62 31…”

Section: Pd-l1 Expression and Clinical Roles In B-cell Lymphomasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

Xu-Monette

Zhou

Young

2018

Blood

349

306

View full text Add to dashboard Cite

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“…[8][9][10] Recent studies have illustrated the amplification and expression of PD-L1 in DLBCL through fluorescence in-situ hybridisation (FISH) and immunohistochemistry (IHC). [11][12][13] These studies showed that high PD-L1 protein expression is correlated with a poor prognosis of DLBCL patients. However, PD-L1 protein levels may differ and show great variation, according to the antibodies and platforms used, the diverse cutoffs used for positivity, and the complicated upstream regulation.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have demonstrated that PD‐L1 is up‐regulated and results in a poorer prognosis in some types of cancer, including ovarian cancer, oesophageal cancer, and hepatocellular cancer . Recent studies have illustrated the amplification and expression of PD‐L1 in DLBCL through fluorescence in‐situ hybridisation (FISH) and immunohistochemistry (IHC) . These studies showed that high PD‐L1 protein expression is correlated with a poor prognosis of DLBCL patients.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…13,14 In addition, PD-L1 expression on tumor cells and/or macrophages were linked to increased PD-1 + tumor-infiltrating lymphocyte (TIL) infiltration. 15,16 PCNS-DLBCL is an entity distinct from systemic DLBCL in terms of its clinical, pathological, and genetic features. 17 Moreover, because it resides in an immune-privileged site, PCNS-DLBCL may have a distinct immune microenvironment.…”

Section: Introductionmentioning

confidence: 99%

High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

et al. 2019

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We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30% of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30% of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+ . PD-1 + and CD8 + tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7%) were tPD-L1+ and 47 cases (48%) were tmPD-L1+ . The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1− cases (CD8 + , P= .050; PD-1 + , P= .019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8 + and PD-1 + TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival (P= .026), and those with increased CD8 + or PD-1 + TILs tended to have a better overall survival (P= .081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1 + TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8 + or PD-1 + TILs had the worst prognosis, and tPD-L1− patients with a large number of CD8 + or PD-1 + TILs had the best prognosis. In validation group, increased CD8 + or PD-1 + TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8 + and PD-1 + TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL. ARTICLE HISTORY

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CD274 (PD‐L1)/PDCD1 (PD‐1) expression in de novo and transformed diffuse large B‐cell lymphoma

Cited by 24 publications

References 10 publications

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

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

High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

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CD274 (PD‐L1)/PDCD1 (PD‐1) expression in de novo and transformed diffuse large B‐cell lymphoma

Cited by 24 publications

References 10 publications

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

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

High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

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High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system