Immune checkpoint molecule (ICM) (ICM)

Immune checkpoint molecules are a diverse group of cell surface proteins that play a critical role in regulating the immune system's response to self and non-self antigens (Pardoll, 2012, Nature Reviews Cancer). These molecules function as either co-inhibitory or co-stimulatory signals, acting as "brakes" or "accelerators" to maintain immune homeostasis and prevent autoimmunity (Ribas & Wolchok, 2018, Science). In many cancers, tumors upregulate inhibitory checkpoint ligands, such as Programmed death-ligand 1 (PD-L1), to suppress T-cell activity and evade immune surveillance (NCI, 2023). Therapeutic strategies primarily involve the use of monoclonal antibodies, known as checkpoint inhibitors, which block these inhibitory pathways (e.g., PD-1, CTLA-4, LAG-3) to restore and enhance anti-tumor immunity (Postow et al., 2018, NEJM). While these treatments have revolutionized oncology, they are often associated with immune-related adverse events (irAEs) resulting from the non-specific activation of the immune system against healthy tissues (Darvin et al., 2018, Exp Mol Med). Ongoing research focuses on identifying novel checkpoints and developing combination therapies to overcome resistance and improve patient outcomes (Sharma et al., 2017, Cell).

Other names

Immune checkpointCheckpoint proteinCo-inhibitory moleculeCo-stimulatory moleculeCheckpoint receptorCheckpoint ligand

Immune checkpoint molecules regulate immune activation through ligand-receptor interactions that either inhibit or stimulate T-cell signaling. Therapeutic checkpoint inhibitors are primarily monoclonal antibodies that block inhibitory pathways (e.g., PD-1/PD-L1 or CTLA-4), thereby "releasing the brakes" on the immune system to allow for an effective anti-tumor response (Pardoll, 2012, Nature Reviews Cancer; Ribas & Wolchok, 2018, Science).