Immune checkpoint inhibitors in cancer therapy: The leading role of the endocrinologist

The endocrine, immune, and nervous systems have a close functional relation from the embryonic development until the end of life, nevertheless this important homeostasis can be altered by any stressors such as infections, autoimmune diseases, neoplasms or medications. Immune checkpoint inhibitors (ICPi) have relatively recently emerged as a promising treatment option for several cancers, including advanced melanoma, non–small cell lung cancer, renal cell carcinoma, and colorectal cancer. ICPi target immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1). ICPi modulates the immune system with the aim of eradicating cancer cells, but despite their acknowledged anti-cancer efficacy, they can increase the risk of developing autoimmune disorders. In this fashion, the same mechanisms that support tumor regression may favor autoantigen-mediated cytotoxicity and the production of T-cell-dependent autoantibodies. Importantly, patients on ICPi may develop endocrine adverse events, even after months or years from the final dose of ICPi, affecting a wide variety of glands. These endocrine adverse events include hypophysitis, diabetes mellitus, hypo and hyperthyroidism, and, adrenal insufficiency. Such toxicities may complicate the clinical course and prognosis of patients, increasing morbidity and mortality if not promptly identified and treated, as they can be life threatening and irreversible