Immune Checkpoint Inhibition in Classical Hodgkin Lymphoma: From Early Achievements towards New Perspectives

Goycoechea, Diego de; Stalder, Grégoire; Martins, Filipe; Duchosal, Michel A.

doi:10.1155/2019/9513701

Cited by 20 publications

(21 citation statements)

References 90 publications

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“…The EBV derived latent membrane protein 1 (LMP1) mimics CD40 and activates NF-κβ signaling which consequently induces PD-L1 expression in a NF-κβ-dependent manner. LMP1 is also known to mediate the up-regulation of PD-L1 through activation of other pathways, i.e., AP-1 and JAK/STAT [ 13 , 55 , 56 , 57 ]. Despite the frequency of EBV infection, cHL cases associated with EBV (EBV POS ) have been reported to have the same degree of PD-L1/PD-L2 copy number alterations as non-EBV associated cases (EBV NEG ) [ 13 ].…”

Section: Immune Checkpoint Molecules In Classical Hodgkin Lymphomamentioning

confidence: 99%

PD-1 and LAG-3 Checkpoint Blockade: Potential Avenues for Therapy in B-Cell Lymphoma

Tobin

Bednarska

Campbell

et al. 2021

Cells

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The dependence of cancer on an immunotolerant tumor microenvironment (TME) is well established. Immunotherapies that overcome tumor-induced immune suppression have been central to recent advancements in oncology. This is highlighted by the success of agents that interrupt PD-1 mediated immune suppression in a range of cancers. However, while PD-1 blockade has been paradigm-shifting in many malignancies, the majority of cancers show high rates of primary resistance to this approach. This has led to a rapid expansion in therapeutic targeting of other immune checkpoint molecules to provide combination immune checkpoint blockade (ICB), with one such promising approach is blockade of Lymphocyte Activation Gene 3 (LAG-3). Clinically, lymphoproliferative disorders show a wide spectrum of responses to ICB. Specific subtypes including classical Hodgkin lymphoma have demonstrated striking efficacy with anti-PD-1 therapy. Conversely, early trials of ICB have been relatively disappointing in common subtypes of Non-Hodgkin lymphoma. In this review, we describe the TME of common lymphoma subtypes with an emphasis on the role of prominent immune checkpoint molecules PD-1 and LAG3. We will also discuss current clinical evidence for ICB in lymphoma and highlight key areas for further investigation where synergistic dual checkpoint blockade of LAG-3 and PD-1 could be used to overcome ICB resistance.

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Section: Immune Checkpoint Molecules In Classical Hodgkin Lymphomamentioning

confidence: 99%

PD-1 and LAG-3 Checkpoint Blockade: Potential Avenues for Therapy in B-Cell Lymphoma

Tobin

Bednarska

Campbell

et al. 2021

Cells

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“…In EBV-positive cases, three EBV proteins, EBNA1, LMP1, and LMP2A, are expressed (latency II). HRS cells are equipped with mechanisms to escape immune surveillance, including the downregulation of MHC class I and II, and the overexpression of CTL suppressor molecules, such as PD-L1, PD-L2, TGF-β, IL-10, Gal-1, Fas-L, and Treg-attracting chemokines ( 30 ). HRS cells originate from GC B cells.…”

Section: Hodgkin's Lymphomamentioning

confidence: 99%

Pathologically Relevant Mouse Models for Epstein–Barr Virus–Associated B Cell Lymphoma

Huang

Yasuda

2021

Front. Immunol.

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The Epstein–Barr virus (EBV) is endemic in humans and can efficiently transform infected B cells under some circumstances. If an EBV carrier experiences immune suppression, EBV+ B cells can turn into lymphoblasts and exhibit growth expansion that may cause lymphoproliferative diseases which often develop into lymphoma. Our immune system conducts surveillance for EBV+ B cells in order to block spontaneous tumor formation. Here, we summarize the EBV products involved in tumorigenesis, EBV-associated lymphomas, and pathologically relevant mouse models. Preclinical mouse models for a range of EBV-associated diseases not only clear the path to new therapeutic approaches but also aid in our understanding of the nature of lymphomagenesis and immune surveillance.

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“…Many trials of immune checkpoint inhibition, also having a focus on the TME, have been performed and are currently ongoing; we refer to other excellent reviews regarding a concise overview on this topic 16,17 as well as graphical visualization of the relationships between TME‐cells, lymphoma cells and proteins involved in checkpoint inhibition 5,18 …”

Section: Short Insight Into the Function Of Immune Checkpoint Proteinsmentioning

confidence: 99%

The tumor microenvironment of lymphomas: Insights into the potential role and modes of actions of checkpoint inhibitors

Menter

Tzankov

Dirnhofer

2020

Hematological Oncology

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The tumor microenvironment (TME) – a term comprising non‐neoplastic cells and extracellular matrix as well as various cytokines, chemokines, growth factors, and other substances in the vicinity of tumor cells – is an integrative part of most tumors including lymphomas. Interactions between lymphoma cells and the TME are vital for survival and proliferation of the former. In addition, lymphoma cells often reprogram the TME to protect them from defense mechanisms of the host's immune system. In this review, we will introduce the role of the tumor microenvironment (TME) for lymphoma cells looking at direct cell–cell interactions as well as cytokine‐related communications. The immunomodulative/immunosuppressive role of the TME is more and more coming into the focus of potential new targeted therapies, and thus a special attention will be given to the interactions of immune checkpoints such as programed cell death protein 1 and L1 (PD‐1/PD‐L1), T‐cell immunoglobulin and mucin‐domain containing protein‐3 (TIM‐3), lymphocyte‐activation gene 3 (LAG‐3), and cytotoxic T‐lymphocyte‐associated protein‐4 (CTLA4) with the TME, as well as their expression by both lymphoma cells and cells of the TME. Aspects of the TME will be discussed for indolent and aggressive B‐cell lymphomas, Hodgkin lymphomas, and T‐cell lymphomas. In addition, the potential influence of other immunomodulators such as lenalidomide will be briefly touched. The complex role of the TME is in the focus of new therapeutic options. In order to exploit its full therapeutic potential, however, a thorough understanding of TME biology and interaction between lymphoma cells and the TME, as well as the host's immune system and the TME is necessary.

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Immune Checkpoint Inhibition in Classical Hodgkin Lymphoma: From Early Achievements towards New Perspectives

Cited by 20 publications

References 90 publications

PD-1 and LAG-3 Checkpoint Blockade: Potential Avenues for Therapy in B-Cell Lymphoma

PD-1 and LAG-3 Checkpoint Blockade: Potential Avenues for Therapy in B-Cell Lymphoma

Pathologically Relevant Mouse Models for Epstein–Barr Virus–Associated B Cell Lymphoma

The tumor microenvironment of lymphomas: Insights into the potential role and modes of actions of checkpoint inhibitors

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