Abstract
Treatment with immune checkpoint inhibitors has shown efficacy against a variety of cancer types. The effects of nivolumab and pembrolizumab on lung cancer have been reported, and further therapeutic advances are ongoing. The side effects of immune checkpoint inhibitors are very different from those of conventional cytocidal anticancer drugs and molecular targeted drugs, and they involve various organs such as the digestive and respiratory organs, thyroid and pituitary glands, and skin. The generic term for such adverse events is immune-related adverse events (irAEs). They are relatively infrequent, and, if mild, treatment with immune checkpoint inhibitors can be continued with careful control. However, early detection and appropriate treatment are critical, as moderate-to-severe irAEs are associated with markedly reduced organ function and quality of life, with fatal consequences in some cases. Of these, endocrinopathies caused by immune checkpoint inhibitors are sometimes difficult to distinguish from nonspecific symptoms in patients with advanced cancer and may have serious outcomes when the diagnosis is delayed. Therefore, it is necessary to anticipate and appropriately address the onset of endocrinopathies during treatment with immune checkpoint inhibitors. Here, we present a review of endocrine disorders caused by immune checkpoint inhibitor treatment.
Highlights
In 2011, the Food and Drug Administration (FDA) approved the immune checkpoint inhibitor (ICI) ipilimumab, an anti-cytotoxic T-lymphocyte antigen-4 antibody, for the treatment of malignant melanoma
With regard to the pathogenesis of primary adrenal insufficiency caused by ICI treatment, adrenal autoantibodies have been detected in one case of pembrolizumab-induced adrenal insufficiency, several points remain to be clarified [31]
Endocrine dysfunction is a frequent immune-related adverse events (irAEs) associated with ICI treatment
Summary
In 2011, the Food and Drug Administration (FDA) approved the immune checkpoint inhibitor (ICI) ipilimumab, an anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibody, for the treatment of malignant melanoma. Anti-CTLA-4 antibodies bind to CTLA-4 and block the inhibitory receptors of activated T-cells, exerting antitumor effects They bind to the surface CTLA-4 in regulatory T-cells (Tregs), reducing the immunosuppressive function of Tregs and enhancing tumor immune responses [4]. While ICIs exhibit antitumor effects via a novel mechanism, immune adjustments do not work correctly in all cases, and side effects resembling autoimmune and inflammatory diseases have been reported. These types of adverse events, termed immune-related adverse events (irAEs), are characteristic side effects of ICI treatment, being distinct from the side effects of conventional anticancer drug treatment [9]. We present a review of endocrine disorders caused by ICI treatment
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