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LAG3: a novel immune checkpoint expressed by multiple lymphocyte subsets in diffuse large B-cell lymphoma
Colm Keane1,2, Soi C Law1, Clare Gould3
1Mater Research, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Blood Advances
|April 9, 2020
Summary
High expression of Lymphocyte-activation gene 3 (LAG3) in diffuse large B-cell lymphoma (DLBCL) correlates with poor patient survival. LAG3 is found on T cells, B cells, and macrophages, often co-expressed with other immune checkpoints.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Blockade of the PD-1 axis shows limited efficacy in diffuse large B-cell lymphoma (DLBCL).
- Data on Lymphocyte-activation gene 3 (LAG3) in DLBCL are scarce.
- Understanding immune checkpoint expression is crucial for improving DLBCL treatment.
Purpose of the Study:
- To investigate the impact of LAG3 gene expression and protein distribution in DLBCL.
- To determine the prognostic significance of LAG3 in DLBCL patients.
- To explore the relationship between LAG3, PD-1/PD-L1, and patient outcomes.
Main Methods:
- Digital gene expression analysis of LAG3 in 309 DLBCL patients.
- Immunohistochemistry and flow cytometry for cellular distribution of LAG3 protein.
- Digital spatial protein analysis to confirm protein expression in the tumor microenvironment.
Main Results:
- LAG3 expression was highest on CD4+ regulatory T cells (Tregs) and CD8+ T cells within tumor-infiltrating lymphocytes (TILs).
- LAG3 was also expressed on a subset of malignant B cells and tumor-associated macrophages (TAMs).
- High LAG3 gene expression was independently associated with inferior progression-free and overall survival in DLBCL patients.
- Co-expression of LAG3 and PD-L1 was linked to significantly worse outcomes compared to LAG3-low/PD-L1-high patients.
Conclusions:
- LAG3 is frequently expressed on immune cells and malignant B cells in DLBCL.
- High LAG3 expression is a significant independent predictor of poor prognosis in DLBCL.
- LAG3, particularly in combination with PD-L1, represents a potential therapeutic target and prognostic biomarker in DLBCL.
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