In this review, we will delve into the PD-1 signaling pathway in T-cells to highlight the mechanism of action of ICIs, the cellular functions altered by the PD-1 cascade, and the emerging understanding of irAEs resulting from the use of checkpoint inhibitors and aim to bridge the gap between the use of ICIs, irAEs, and primary autoimmunity. This evidence concerns the gene PDCD1 and Autoimmunity.