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Immune checkpoints are a normal part of the immune system. They prevent an immune response from being so strong that it destroys healthy cells. Immune checkpoints engage when proteins on the surface of T cells recognize and bind to partner proteins on other cells, such as some tumor cells. When the checkpoint and partner proteins bind together, they send an “off” signal to the T cells. This can prevent the immune system from destroying the cancer.

Immunotherapies called immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This prevents the “off” signal from being sent, allowing the T cells to kill cancer cells. The best studied immune checkpoint proteins are CTLA-4 and PD-1 on T-cells and PD-L1 on cancer cells. In 2018, James Allison and Tasuku Honjo were awarded the Nobel prize for the discovery of CTLA-4 and PD-1/PD-L1.

Checkpoint inhibitors are monoclonal antibodies, and they are a major tool in current immunotherapy of solid tumors. In fact, Merck’s check point inhibitor, Keytruda (anti-PD1) was the best-selling anti-cancer drug in 2022. For more details, the American Cancer Society presents an excellent summary on the checkpoint inhibitors currently used in cancer therapy.