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LAG3 (CD223) and autoimmunity: Emerging evidence
Suiyuan Hu1, Xu Liu1, Tianding Li2
1Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
Abstract:
Immune checkpoint molecules play pivotal roles in maintaining the immune homeostasis. Targeting these molecules, such as the classical Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed Cell Death Protein 1 (PD1), achieves great success in treating cancers. However, not all the patients respond well. This urges the immunologists to identify novel immune checkpoint molecules. Lymphocyte activation gene-3 (LAG3; CD223) is a newly identified inhibitory receptor. It is expressed on a variety of immune cells, including CD4+ T cells, CD8+ T cells, Tregs, B cells, and NK cells. Its unique intracellular domains, signaling patterns as well as the striking synergy observed in its targeted therapy with anti-PD1 indicate the important role of LAG3 in maintaining immune tolerance. Currently, a variety of agents targeting LAG3 are in clinical trials, revealing great perspectives in the future immunotherapy. In this review, we briefly summarize the studies on LAG3, including its structure, isoforms, ligands, signaling, function, roles in multiple diseases, as well as the latest targeted therapeutic advances, with particular concern on the potential association of LAG3 with autoimmune diseases.
Insights
Lymphocyte activation gene-3 (LAG3) is a novel immune checkpoint molecule. Targeting LAG3 offers new immunotherapy perspectives, especially in combination with anti-PD1 therapy, for various diseases.
Area of Science:
- Immunology and Cancer Biology
- Molecular and Cellular Biology
Background:
- Immune checkpoints like CTLA4 and PD1 are crucial for immune homeostasis and cancer treatment.
- Limited patient response to current therapies necessitates identifying novel immune checkpoints.
- Lymphocyte activation gene-3 (LAG3) is an emerging inhibitory receptor expressed on multiple immune cells.
Purpose of the Study:
- To review the current understanding of Lymphocyte Activation Gene-3 (LAG3).
- To explore LAG3's structure, isoforms, ligands, signaling, and function.
- To discuss LAG3's role in diseases and its potential as an immunotherapy target.
Main Methods:
- Comprehensive literature review of studies on LAG3.
- Analysis of LAG3's expression patterns and cellular functions.
- Evaluation of LAG3's role in immune tolerance and disease pathogenesis.
Main Results:
- LAG3 exhibits unique signaling properties and synergistic effects with anti-PD1 therapy.
- LAG3 is implicated in maintaining immune tolerance and is a target in ongoing clinical trials.
- Emerging evidence suggests LAG3's association with autoimmune diseases.
Conclusions:
- LAG3 represents a promising target for novel immunotherapies, particularly in combination treatments.
- Further research into LAG3's role in autoimmune diseases is warranted.
- Targeting LAG3 holds significant potential for advancing cancer immunotherapy and managing immune-related disorders.
