PD-1 and LAG-3 Checkpoint Blockade: Potential Avenues for Therapy in B-Cell Lymphoma.
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| Abstract |
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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| Authors | Joshua W D Tobin, Karolina Bednarska, Ashlea Campbell, Colm Keane |
| Journal | Cells (Cells) Vol. 10 Issue 5 (05 10 2021) ISSN: 2073-4409 [Electronic] Switzerland |
| PMID | 34068762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review) |
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