T-cell immunoglobulin and mucin-domain containing-3 ligand (Tim-3 ligand) (Tim-3 ligand)

T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) ligands are a group of structurally diverse molecules—including Galectin-9, Phosphatidylserine (PtdSer), High mobility group box 1 (HMGB1), and Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)—that bind to the Tim-3 receptor to regulate immune homeostasis (Wolf et al., Nature Reviews Immunology, 2020). These ligands are primarily involved in the negative regulation of Th1 and Th17 immune responses and the induction of T-cell exhaustion, a state of dysfunction common in chronic infections and cancer (Zhu et al., Nature Immunology, 2005). For example, Galectin-9 triggers T-cell death upon binding, while PtdSer facilitates the recognition and clearance of apoptotic cells (DeKruyff et al., Journal of Immunology, 2010). In the tumor microenvironment, the overexpression of these ligands contributes to immune evasion by suppressing the activity of tumor-infiltrating lymphocytes and dendritic cells (Chiba et al., Nature Immunology, 2012). Consequently, the Tim-3/ligand axis has become a major focus for cancer immunotherapy, with several monoclonal antibodies in clinical trials designed to block these interactions and restore anti-tumor T-cell activity (Huang et al., Nature, 2015). While most current clinical candidates, such as sabatolimab, target the Tim-3 receptor itself to prevent ligand binding, the ligands themselves are increasingly viewed as distinct therapeutic targets to modulate the immune environment.

Other names

Galectin-9PhosphatidylserineHigh mobility group box 1Carcinoembryonic antigen-related cell adhesion molecule 1LGALS9PtdSerHMGB1CEACAM1HAVCR2 ligand

Blockade of the interaction between Tim-3 and its ligands to prevent inhibitory signaling and restore effector T-cell function.