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Lymphocyte activation gene 3 (LAG3) is a T cell inhibitory receptor that promotes tumor cell immune escape and is a potential target for cancer diagnostic and immunotherapeutic applications.
The immunomodulatory protein, Lymphocyte activation gene 3 (LAG3) (CD223) was discovered over 30 years ago. As a novel member of the immunoglobulin (Ig) superfamily. LAG3 is a transmembrane protein with four extracellular Ig-like domains that show approximately 20% amino acid homology with CD4. Surface expression of the LAG3 receptor is induced on CD4+ and CD8+ T cells upon antigen stimulation, and functions as a negative regulator of T cell cytotoxicity. And the inhibitory function of LAG3 strongly correlates with the level of surface expression and subsequently, high LAG3, on tumor infiltrating lymphocytes, is associated with a poor prognosis. Preclinical and early clinical trials have indicated that active LAG3 promotes tumor cell immune escape. Inhibition of LAG3 restores T cell activity, and is synergistic with inhibition of PD-1, making it a prime target for immunotherapy.