Thus, while the PD-L1/PD-1 pathway is a master regulator of immune-tolerance and can be taken advantage of for the augmentation of anti-tumor immunity, clinical transplantation demonstrates that it is a double-edged sword in that it is also required for the maintenance of T cell tolerance to prevent autoimmunity in cancer patients as well as alloimmunity following HCT. The gene discussed is PDCD1; the disease is neoplasm.