RESUMO
Immunomodulatory agents targeting immune checkpoints are now the state-of-the-art for the treatment of many cancers, but at the same time have led to autoimmune side effects, including autoimmune diabetes: immune checkpoint inhibitor-induced diabetes (CPI-DM). Emerging research shows the importance of preexisting autoimmune disease risk that has been identified through genetics, and autoantibodies. Key associated clinical findings also include increased levels of lipase before diagnosis suggesting that the inflammatory process in the pancreas extends beyond the islets of Langerhans. There is selectivity for the blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) for this adverse event, consistent with the role of this checkpoint in maintaining tolerance to autoimmune diabetes.
RESUMO
Following the seminal discovery of insulin a century ago, treatment of individuals with type 1 diabetes (T1D) has been largely restricted to efforts to monitor and treat metabolic glucose dysregulation. The recent regulatory approval of the first immunotherapy that targets T cells as a means to delay the autoimmune destruction of pancreatic ß-cells highlights the critical role of the immune system in disease pathogenesis and tends to pave the way for other immune-targeted interventions for T1D. Improving the efficacy of such interventions across the natural history of the disease will probably require a more detailed understanding of the immunobiology of T1D, as well as technologies to monitor residual ß-cell mass and function. Here we provide an overview of the immune mechanisms that underpin the pathogenesis of T1D, with a particular emphasis on T cells.