Neoantigens and Microenvironment in Type 1 Diabetes: Lessons from Antitumor Immunity.
Type 1 diabetes (T1D) is characterized by the selective and progressive destruction of insulin-producing beta cells by the immune system. An incomplete thymic selection against self-reactive islet antigens partly explains how these T cells reach the periphery and become diabetogenic. Increasing evidence suggest that beta cells themselves also participate to their own demise by generating neoepitopes that could be recognized by the immune surveillance machinery. In this regard, these T cells eradicate self-tissue by mechanisms analogous to a classical antitumor response. Cancer immunotherapy has exploited mutations and transcriptional and translational errors to trigger a specific antitumor response. In this opinion article, we aim at merging insight in antitumor immunology and autoimmunity to reveal processes that had previously been ignored to create beta cell-specific neoantigens.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Maria J L
MJL
Kracht
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Arnaud
A
Zaldumbide
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Department of Diabetes Immunology, Diabetes and Metabolism Research Institute at the Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. Electronic address: boroep@lumc.nl.
Bart O
BO
Roep
D000818:Animals; D015551:Autoimmunity / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
autoreactive T cells; cancer; diabetes; immunotherapy; neoantigens; pancreatic beta cells