Figure 1.

Role of immune checkpoints in antitumor immune responses and endocrine adverse events, induced by immune checkpoint inhibitors. CTLA-4 competes with CD80/CD86 to prevent excessive T-cell activation, while the activation of the PD-1/PD-L1 axis keeps T-cell in an anergic state. Furthermore, LAG-3 interacts with MHC, upregulating the function of T-cells and downregulating TCR signal transduction. Inhibition of these immune checkpoints induced by ICIs prevents inhibition signals, and recognizes T-cells to kill cancer cells. On the other hand, this process can also lead to a reduced self-tolerance against other tissues, thus favoring autoimmune events, including endocrine ones, at different levels. APC: antigen-presenting cell; B7: CD80/CD86; CTLA-4: cytotoxic T-lymphocyte-associated protein; LAG-3: lymphocyte-activation gene 3; MHC: major histocompatibility complex; PD-1: programmed cell death protein 1; PD-L1: programmed death ligand 1; TCR: T cell receptor.