Discovery of PD-1

The discovery of PD-1, short for programmed cell death protein 1, identified a receptor on T cells and pro-B cells that acts as an immune checkpoint. In 1992, in a screen for genes involved in apoptosis, Yasumasa Ishida, Tasuku Honjo and colleagues at Kyoto University discovered and named PD-1. In 1999 the same group showed that mice lacking PD-1 were prone to autoimmune disease, and concluded that PD-1 is a negative regulator of immune responses. PD-1 binds two ligands, PD-L1 and PD-L2, and suppresses T cell inflammatory activity, which protects against autoimmunity but can also stop the immune system from killing cancer cells. That role led to PD-1 inhibitors, a class of drugs that release the brake and let the immune system attack tumors in certain cancers. The 2018 Nobel Prize in Physiology or Medicine went to James P. Allison and Tasuku Honjo for the discovery of cancer therapy by inhibition of negative immune regulation.