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The Role of Programmed Death-1 in Type 1 Diabetes

  • Pathogenesis of Type 1 Diabetes (A Pugliese and SJ Richardson, Section Editors)
  • Published:
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Abstract

Purpose of Review

Programmed death-1 (PD-1) is an inhibitory receptor that controls T and B cell proliferation and function through interacting with its ligand PD-L1 or PD-L2. PD-1/PD-L1 blockade reboots anti-tumor immunity and is currently used to treat > 15 different types of cancer. However, the response rate is not at 100% and some patients relapse. Importantly, up to 37% of patients treated with PD-1/PD-L1 blocking antibodies develop immune-related adverse events, including overt autoimmunity, such as type 1 diabetes (T1D). Herein, we discuss the role of PD-1, PD-L1, and PD-L2 signaling in pre-clinical models of T1D, including recent work from our laboratory.

Recent Findings

We highlight ongoing efforts to harness PD-1/PD-L1 signaling and treat autoimmunity. We also evaluate studies aimed at defining biomarkers that could reliably predict the development of immune-related adverse events after clinical PD-1/PD-L1 blockade.

Summary

With increasing use of PD-1 blockade in the clinic, onset of autoimmunity is a growing health concern. In this review, we discuss what is known about the role of PD-1 pathway signaling in T1D and comment on ongoing efforts to identify patients at risk of T1D development after PD-1 pathway blockade.

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Acknowledgements

This work was supported by NIH P01 AI35296 (BTF).

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  1. Tijana Martinov

    Present address: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Thomas Building, D3-100, Seattle, WA, 98109, USA

  2. Brian T. Fife and Tijana Martinov contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Center for Immunology, University of Minnesota Medical School, 2101 6th St SE, Wallin Medical Biosciences Building, 3-146, Minneapolis, MN, 55455, USA

    Christopher G. Tucker, Alexander J. Dwyer, Brian T. Fife & Tijana Martinov

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  1. Christopher G. Tucker
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  2. Alexander J. Dwyer
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Correspondence to Brian T. Fife or Tijana Martinov.

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Christopher G. Tucker, Alexander J. Dwyer, and Tijana Martinov each declare no potential conflicts of interest.

Brian T. Fife has a patent pending for Monoclonal antibodies directed to peptide in the context of MHC and methods of making and using monoclonal antibodies; Office: United States of America. Application number: 15952965; application date: 13.04.2018; publication number: 20180298103; publication date: 18.10.2018.

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This article is part of the Topical Collection on Pathogenesis of Type 1 Diabetes

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Tucker, C.G., Dwyer, A.J., Fife, B.T. et al. The Role of Programmed Death-1 in Type 1 Diabetes. Curr Diab Rep 21, 20 (2021). https://doi.org/10.1007/s11892-021-01384-6

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