The Role of Immune Checkpoint Therapy in Propagating Neurologic Immune-Related Adverse Events: Inducing or "Unmasking" Autoimmunity?

In 2010, a novel agent, ipilimumab, demonstrated improved survival rates in patients with previously untreatable metastatic melanoma.1 Ipilimumab was approved by the Food and Drug Administration in 2011 and launched a class of pharmaceuticals that would come to be known as immune checkpoint inhibitors (ICIs). Normally, the immune system monitors developing malignancies as they acquire progressive mutations and eliminates them through a process of immunoediting or immune surveillance.2 Select tumors learn to coopt self-tolerance mechanisms (immune checkpoints) to evade this immune detection. ICIs inhibit these negative regulators of T-cell activation, unleashing an unchecked immune response. Because this response is not specific to tumor antigens, a host of immune-related adverse events (irAEs) can ensue. Neurologic irAEs are rare3 but provide diagnostic and therapeutic challenges. They also offer important insights into the mechanisms of autoimmunity.

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