Endocrine immune-related adverse effects of immune-checkpoint inhibitors

IntroductionImmune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and the PD-1/PD-L1 pathways. ICI therapy can trigger autoimmune adverse effects, known as immune-related Adverse Events (irAEs).Areas coveredThis review focuses on irAEs which affect the endocrine system. This review elucidates the pathways used by these drugs with a focus on the hypothetical pathogenesis at their basis. In fact, the pathophysiology of irAEs concerns the possibility of an interaction between cellular autoimmunity, humoral immunity, cytokines, chemokines, and genetics. The endocrine irAEs examined are thyroid dysfunctions, immune related-hypophysitis, diabetes, peripheral adrenal insufficiency, and hypoparathyroidism.Expert opinionThere is still much to investigate in endocrine irAES of checkpoint inhibitors. In the future, checkpoint inhibitors will be increasingly utilized therapies, and therefore it is crucial to find the proper diagnostic-therapeutic program for irAEs, especially as endocrine irAEs are nonreversible and require lifelong replacement therapies.

Automated summary

Immune-checkpoint inhibitor therapy can modulate the immune response against cancer, but it can also trigger immune-related adverse events (irAEs). This review focuses on irAEs affecting the endocrine system, including thyroid dysfunctions, immune-related hypophysitis, diabetes, adrenal insufficiency, and hypoparathyroidism.