Figure 2. Role of Lymphocyte activation gene 3 (LAG3) in the tumor microenvironment (TME).
Left: LAG3 homodimers colocalize to T cell receptor (TCR)/CD3 and inhibit downstream signaling. LAG3 function can be modulated by shedding via a disintegrin and metalloproteinase (ADAM) 10/17 to release soluble LAG3 (sLAG3). Middle: major histocompatibility complex II (MHCII) is the canonical ligand of LAG3. The glutamic acid–proline-rich (EP) motif of LAG3 causes disassociation of Lck from CD4 and CD8 coreceptors to inhibit T cell signaling. Right: FGL1 expressed on tumor cells or secreted (sFLG1) can bind LAG3 to attenuate T cell function. Abbreviation: APC, antigen-presenting cell.