2018 Nobel Prize in medicine awarded to cancer immunotherapy: Immune checkpoint blockade – A personal account

James P Allison and Tasuku Honjo were awarded the 2018 Nobel Prize in Physiology or Medicine for the development of a revolution in cancer therapy 1 : immune checkpoint blockade.This is a truly well-deserved honor for both Allison and Honjo.The immune system has multiple levels of brakes, known as immune checkpoints, to negatively downregulate activation and function of T cells and other immune cells.Immune checkpoints are important mechanisms for preventing the immune system from attacking the host's own cells.Jim's original idea that the temporary relief of immune checkpoints could mobilize the immune system to attack tumors was not popular.When I joined Jim's lab as a postdoctoral fellow in 2000 (Fig. 1), most people in the field did not believe cancer immunotherapy would work in the clinic.The landmark paper published in 1996 experimentally demonstrated Jim's idea for the first time that a monoclonal antibody against CTLA-4, one of the major immune checkpoints, blocked CTLA-4 function and enhanced the anti-tumor immunity, which led to a cure of cancer in mouse models.2 A monoclonal antibody therapy against human CTLA-4 was approved by the Food and Drug Administration (FDA) in 2011 to treat malignant melanoma, 3 which was the first immune checkpoint inhibitor in cancer therapy.Honjo originally cloned PD-1 in 1992 4 and later showed PD-1 as another important immune checkpoint of T cells.5 Subsequently Lieping Chen in 1999 and Gordon J Freeman in 2000 identified and characterized the