Immune Checkpoint Molecules, Personalized Immunotherapy, and Autoimmune Diabetes

Trends Mol Med. 2018 Nov;24(11):931-941. doi: 10.1016/j.molmed.2018.08.005. Epub 2018 Sep 17.

Abstract

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.

Keywords: PD-L1; PD1; immune checkpoints; indoleamine 2,3-dioxygenase 1 (IDO1); personalized therapy; type 1 diabetes (T1D).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmunity / drug effects*
  • B7-H1 Antigen / metabolism
  • Biomarkers*
  • CTLA-4 Antigen / metabolism
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / therapy*
  • Humans
  • Immune Tolerance
  • Immunomodulation / drug effects*
  • Immunotherapy* / adverse effects
  • Immunotherapy* / methods
  • Molecular Targeted Therapy* / methods
  • Precision Medicine* / methods
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • Biomarkers
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor