The Role of Checkpoint Inhibitors in Autoimmune Diseases: Similarities and Differences Compared with Cancer.

ABSTRACT

Programmed cell death-1 (PD-1) immunoinhibitory receptor expression is found on T cells, B cells, natural killer (NK) cells, and myeloid cells. Upon activation of T cells through peptide-major histocompatibility complex (MHC) engagement of the T cell receptor and costimulatory signaling, checkpoints including PD-1 are activated to regulate T cells. Since decreased expression of PD-1 in mice model was found to be associated with breakdown of peripheral tolerance, and demonstrated autoimmune disease characteristic, this receptor may be important therapeutic target for autoimmunity. In addition, decreased NK cell numbers and cytotoxicity in peripheral blood and altered expression of activating receptors and cytokine secretion of NK cells was seen in autoimmune disease patients. Therefore, in this review we discuss the relevance of PD-1 function in NK and T cells in autoimmunity, and demonstrate similarities and differences of its function in autoimmune diseases and cancer. Thus, PD-1 can be targeted to treat each disease entity accordingly. In cancer, the function of PD-1 can be blocked in order to enhance immune activation, whereas in autoimmune diseases it can be enhanced to block heightened immune function. However, we are far from understanding the exact functioning of this receptor in a complex tissue microenvironment, and further studies are required to establish its function at different stages of the disease, and at different stages of the maturation of immune effectors.