Catching up with solid tumor oncology: what is the evidence for a prognostic role of programmed cell death-ligand 1/programmed cell death-1 expression in B-cell lymphomas?

McClanahan, Fabienne; Sharp, T. G.; Gribben, John G.

doi:10.3324/haematol.2016.145904

Cited by 6 publications

(4 citation statements)

References 82 publications

(133 reference statements)

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“…68 Together, these data suggest that PD-1 expression and clinical roles vary across and within B-cell lymphoma entities. However, differences may also result from methodologic (eg, assessed by PD-1 1 cell numbers, percentage expression, or staining intensities; by numbers of PD-1 1 TILs or numbers of PD-1 1 T cells; by percentage of all cells or T cells; by tissue expression or peripheral expression; or by immunohistochemistry or flow cytometry) and technical (use of different antibodies and positivity cutoffs) disparities among studies, 79 illustrating the challenge in assessing the dynamic tumor microenvironment and T-cell responses. Similar issues may exist in clinical studies of PD-1 expression as a biomarker for PD-1 blockade therapy.…”

Section: Introductionmentioning

confidence: 99%

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

Xu-Monette

Zhou

Young

2018

Blood

337

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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Section: Introductionmentioning

confidence: 99%

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

Xu-Monette

Zhou

Young

2018

Blood

337

306

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“…To date, few data are available on RS regarding the cellular interactions mediating the immunological synapse around the molecular surface marker PD-1 and its ligand PD-L1 ( 83 , 104 , 108 ). Here we will focus on PD-1 and PD-L1 deregulations in the context of RS, both on tumor B-cells and microenvironment cells, and the diagnostic and prognostic impact of the negative bi-directional interaction between these cells.…”

Section: Pd-1/pd-l1/pd-l2 Interplay Deregulation By Malignant B-cellsmentioning

confidence: 99%

“…In B-cell neoplasms, the PD-1/PD-L1 axis has been widely explored. There is a correlation between PD-1 and PD-L1 expression levels and prognosis ( 58 , 83 , 91 , 93 , 108 ) as well as potential for therapeutic purposes ( 58 , 74 , 83 , 114 ). The first indication in which PD-1 and PD-L1 inhibitors have been approved to date is relapsed or refractory classical HL after autologous stem cell transplantation (SCT) and treatment with Brentuximab-Vedotin.…”

Section: Ensuing Therapeutic Options In Rsmentioning

confidence: 99%

Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome

et al. 2020

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IntroductionRichter Syndrome (RS) is defined as the development of an aggressive lymphoma in the context of Chronic Lymphocytic Leukemia (CLL), with a Diffuse Large B-Cell Lymphoma (DLBCL) histology in 95% cases. RS genomic landscape shares only a few features with de novo DLBCLs and is marked by a wide spectrum of cytogenetic abnormalities. Little is known about RS microenvironment. Therapeutic options and efficacy are limited, leading to a 12 months median overall survival. The new targeted treatments usually effective in CLL fail to obtain long-term remissions in RS.MethodsWe reviewed available PubMed literature about RS genomics, PD-1/PD-L1 (Programmed Death 1/Programmed Death Ligand 1) pathway triggering and subsequent new therapeutic options.ResultsData from about 207 patients from four landmark papers were compiled to build an overview of RS genomic lesions and point mutations. A number of these abnormalities may be involved in tumor microenvironment reshaping. T lymphocyte exhaustion through PD-L1 overexpression by tumor cells and subsequent PD-1/PD-L1 pathway triggering is frequently reported in solid cancers. This immune checkpoint inhibitor is also described in B lymphoid malignancies, particularly CLL: PD-1 expression is reported in a subset of prolymphocytes from the CLL lymph node proliferation centers. However, there is only few data about PD-1/PD-L1 pathway in RS. In RS, PD-1 expression is a hallmark of recently described « Regulatory B-cells », which interact with tumor microenvironment by producing inhibiting cytokines such as TGF-β and IL-10, impairing T lymphocytes anti-tumoral function. Based upon the discovery of high PD-1 expression on tumoral B lymphocyte from RS, immune checkpoint blockade therapies such as anti-PD-1 antibodies have been tested on small RS cohorts and provided heterogeneous but encouraging results.ConclusionRS genetic landscape and immune evasion mechanisms are being progressively unraveled. New protocols using targeted treatments such as checkpoint inhibitors as single agents or in combination with immunochemotherapy are currently being evaluated.

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“…Taken together, targeting the immune checkpoint membrane proteins PD-1/PD-L1 seems to be a promising novel treatment option for a selected group of ABC-DLBCL and FL patients. However, it is still debated whether expression of PD-1/PD-L1 is of prognostic value for immune checkpoint inhibition therapy in B-NHL [52,53].…”

Section: Function and Targeting Of Immune Checkpoints Pd-1/pd-l1 In Bmentioning

confidence: 99%

Novel Insights into Membrane Targeting of B Cell Lymphoma

2017

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Standard therapy of patients with B cell non-Hodgkin lymphoma (B-NHL) predominantly consists of chemotherapy combined with anti-CD20 (e.g., rituximab) immunotherapy. However, relapse of aggressive B-NHL occurs frequently, and this may coincide with therapy resistance. This demonstrates the urgent need for exploring new lymphoma-targeted therapies. We review here recent insights in the pathophysiology of B-NHL and discuss CD20 and three alternative membrane targets (B cell receptor, immune checkpoints PD-1/PD-L1, tetraspanin CD37) that are currently in the spotlight for B-NHL treatment. Furthermore, we present a novel concept in which the plasma membrane organization of the lymphoma B cell determines the efficacy of membrane-targeted therapies, and this has consequences for treatment application and clinical outcome in patients with B cell lymphoma.

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Catching up with solid tumor oncology: what is the evidence for a prognostic role of programmed cell death-ligand 1/programmed cell death-1 expression in B-cell lymphomas?

Abstract: © Ferrata Storti Foundationwith other substances.

Cited by 6 publications

References 82 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

Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome

Novel Insights into Membrane Targeting of B Cell Lymphoma

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