The Role of Programmed Death-1 in Type 1 Diabetes

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

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


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. 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.

Original languageEnglish (US)
Article number20
JournalCurrent diabetes reports
Issue number6
StatePublished - Jun 2021

Bibliographical note

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

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.


  • Autoantibodies
  • Autoimmunity
  • Checkpoint blockade
  • PD-L1
  • Programmed death-1
  • Type 1 diabetes
  • Signal Transduction
  • Lymphocyte Activation
  • Humans
  • Diabetes Mellitus, Type 1
  • Neoplasms

PubMed: MeSH publication types

  • Review
  • Journal Article
  • Research Support, N.I.H., Extramural


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