fig2

Figure 2. Multiple interactions of LAG-3 within the TME of HCC have made LAG-3 a potential therapeutic target with the aid of bispecific antibodies targeting both LAG-3 and PD-L1. The confirmed ligands of LAG-3 are MHCII, Galectin-3, LSECtin, and FGL1. MHCII is the principal ligand of LAG-3, showing higher binding affinity than CD4, while LAG-3 is highly glycosylated and can interact with Galectin-3, regulating T cell responses. LAG-3/LSECtin interaction is considered to promote tumor growth through the suppression of the antitumor T cell response, while the interaction of FGL1/LAG-3 is considered to promote tumor immune escape through the inhibition of the antigen-specific T cell. Galectin-3: galactose lectin-3; FGL1: fibrinogen-like protein 1; LSECtin: liver sinusoidal endothelial cell lectin; MHCII: major histocompatibility complex II; APC: antigen-presenting cell; ITAM: immuno-receptor tyrosine-based activation motif; FCγR: receptors for the Fc region of IgG; ERK: extracellular signal-regulated kinase.