Immune Checkpoint Molecules, Personalized Immunotherapy, and Autoimmune Diabetes.

Although significant progress has been made in understanding autoimmunity, no immunotherapy to effectively halt immune-mediated destruction of β cells in type 1 diabetes (T1D) is currently available. For successful immunotherapy it will be necessary to identify novel drug targets as well as robust immunologic biomarkers to predict disease heterogeneity and patient responsiveness. Inhibition of immune checkpoint mechanisms represents a novel and effective strategy in tumor immunotherapy. Because they are fundamental to rewiring immune circuits, the underlying mechanisms could be therapeutically enhanced and used as biomarkers in T1D. We examine here current knowledge of immune checkpoint molecules in T1D. One specific immune checkpoint mechanism, namely tryptophan metabolism, may meet the need for a valid drug target and robust biomarker in the quest for effective and personalized immunotherapy in T1D. Highlights T1D is a heterogeneous autoimmune disease for which an effective cure by immunotherapy has not yet been identified. Immune checkpoint molecules are regulators of the immune system that maintain self-tolerance and prevent autoimmunity. Indoleamine 2,3-dioxygenase 1 (IDO1) is an immune checkpoint enzyme that is defective in patients affected by T1D and is characterized by genetic polymorphism. Restoration of full IDO1 activity can be obtained in vitro by using a blocker of the interleukin-6 receptor (tocilizumab) in peripheral blood mononuclear cells from patients with T1D characterized by a specific IDO1 genotype (rs7820268 C>T). Personalized drug targeting of IDO1 may lead to an effective cure by immunotherapy in patients with T1D. [ABSTRACT FROM AUTHOR]