Immune checkpoint inhibitors associated thyroiditis: mechanisms and clinical outcomes

Background Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment improving prognosis in many cancers. However, ICI often trigger immune-related adverse events (irAEs) that can affect various organ systems, leading to significant clinical challenges. The most frequent irAEs are those affecting the endocrine glands, reported in approximately 10% of treated patients. Thyroid dysfunction is the most common endocrine irAEs, mainly associated with PD-1/PD-L1 blockade therapies. Transient asymptomatic thyrotoxicosis is the most common form of clinical presentation, often followed by hypothyroidism. Interestingly, several studies have demonstrated that irAEs correlate with the response to cancer therapy and with improved overall survival (OS). The mechanisms underlying thyroid irAEs are not fully elucidated but complex interactions between genetic predisposition to thyroid autoimmunity, distinct immune mechanisms and thyroid cell intrinsic mechanisms are thought to drive thyroiditis associated with ICI therapy. Purpose In this review we discuss the latest data on clinical features of thyroid irAEs, proposed mechanisms and their association with improved survival.