LAG3 checkpoint function and its mechanism of action in therapeutic targeting.

LAG3 is an immune inhibitory checkpoint receptor that suppresses T cell activation, proliferation, and effector functions, and its signalling mechanisms remain incompletely defined despite decades of study.

• Why it matters: Persistent disease states link chronic TCR signalling with sustained LAG3 and other inhibitory receptor signalling to T cell dysfunction, creating a need to clarify LAG3 pathways for better targeting.
• What they did: This Review synthesizes recent advances describing tonic signalling, ligand-induced ubiquitination-dependent signalling switches, and LAG3–TCR proximity-mediated suppression, alongside mechanisms of LAG3-blocking antibodies.
• The result: The integrated framework supports improved selection of clinical indications, development of predictive biomarkers, and design of more effective LAG3-targeted therapeutics for oncology and autoimmune disease.

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