Checkpoint-based immunotherapy for autoimmune diseases – Opportunities and challenges

Abstract Immune checkpoint pathways modulate the T cell response to ensure their dual function in maintaining health, eradicating or controlling malignancy and infection, as well as tolerating host autoantigens. Dysregulation of the checkpoint pathways may lead to development of cancer or persistent infection, or alternately, autoimmune diseases. Currently available treatments for autoimmune diseases, such as steroid and nonsteroid immunosuppressive medicines, have limited efficacy. Checkpoint-based immunotherapy, designed to directly block the activation pathway or agitate the inhibitory pathway of autoreactive T cells, is a promising therapeutic strategy for restoring T cell tolerance in autoimmune diseases. A major challenge in developing the checkpoint-based therapy for autoimmune diseases is identifying pathways that will minimize the induction of adverse global immune suppression that impairs the host protective immunity against cancer and microbial pathogens. Therefore research efforts should focus on increasing the organ or antigen specificity of such therapies.