What are immune checkpoints?

Immune checkpoints are a class of regulatory molecules in the immune system that are expressed on immune cells such as T cells and can modulate the intensity and duration of immune responses. Their main function is to prevent excessive activation of the immune system and avoid damage to the body's own tissues, and they are also called "immune sentinels."

In cancer immunology, immune checkpoint molecules play an important role. Tumor cells can exploit these molecules to suppress T cell activity, thereby evading attack by the immune system. For example, the binding of the programmed cell death receptor (PD-1) and its ligands (PD-L1 and PD-L2) can inhibit T cell activity, allowing tumor cells to survive and proliferate.

Other common immune checkpoints include CTLA-4, TIM-3, LAG-3, TIGHT, IDO, etc., which participate in the immune regulatory process through different mechanisms. The discovery and research of immune checkpoints have provided new perspectives and approaches for cancer treatment, particularly in the development and application of immune checkpoint inhibitors.

The mechanism of action of immune checkpoint inhibitors is primarily to block the binding of immune checkpoints to their ligands, relieving the immune function suppression caused by immune checkpoints and reactivating immune cells to exert anti-tumor effects. These inhibitors mainly target key immune checkpoint molecules such as CTLA-4, PD-1, and PD-L1, by activating the patient's immune response to effectively fight against cancer. For example, PD-1 inhibitors can bind to its ligands PD-L1/PD-L2 and transduce inhibitory signals, thereby reducing T cell proliferation and function. If tumor or microenvironmental cells express the ligands for PD-1, it facilitates immune evasion by tumor cells. Anti-PD-1/PD-L1 antibodies can block ligand-receptor binding and restore anti-tumor T cell activity. Similarly, CTLA-4 inhibitors can block the binding of CTLA-4 to B7 molecules, preventing T cell suppression and enhancing T cell activity. In this way, immune checkpoint inhibitors can promote the immune system's attack on tumor cells, helping to treat various types of cancer.