Cancer Immunology, Immunotherapy

, Volume 64, Issue 6, pp 765–767 | Cite as

Anti-programmed cell death-1 therapy and insulin-dependent diabetes: a case report

  • Juan Martin-Liberal
  • Andrew JS Furness
  • Kroopa Joshi
  • Karl S. Peggs
  • Sergio A. Quezada
  • James LarkinEmail author
Original Article


The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. Immune checkpoint inhibitors such as these can induce endocrine adverse events but autoimmune diabetes has not been described to date. However, there is a strong preclinical rationale that supports this autoimmune toxicity. We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. The presence of high serum titres of anti-glutamic acid decarboxylase antibodies together with a suggestive clinical presentation, age of the patient and preclinical data strongly support an autoimmune aetiology of the diabetes. Moreover, the patient was found to have a well-known high-risk human leucocyte antigen type for the development of type 1 diabetes in children, so the PD-1 inhibition is very likely to have triggered the autoimmune phenomenon. Our case suggests that insulin-dependent diabetes might be a rare but important anti-PD-1 immune-related adverse event.


Diabetes Melanoma MK-3475 Nivolumab PD-1 Pembrolizumab 



Anti-glutamic acid decarboxylase


Food and Drug Administration


Human leucocyte antigen


Latent autoimmune diabetes of the adult


Programmed cell death-1


Conflict of interest

James Larkin has received research funding from Pfizer and Novartis. He has also been a consultant for GlaxoSmithKline, Bristol-Myers Squib, Pfizer and Novartis. The rest of the authors have no conflict of interest to disclose.

Informed consent

The patient provided written informed consent for her clinical data to be published in a medical journal.


  1. 1.
    Ansari MJ, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H et al (2003) The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 198(1):63–69CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Guleria I, Gubbels Bupp M, Dada S, Fife B, Tang Q, Ansari MJ et al (2007) Mechanisms of PDL1-mediated regulation of autoimmune diabetes. Clin Immunol 125(1):16–25CrossRefPubMedGoogle Scholar
  3. 3.
    Kochupurakkal NM, Kruger AJ, Tripathi S, Zhu B, Adams LT, Rainbow DB et al (2014) Blockade of the programmed death-1 (PD1) pathway undermines potent genetic protection from type 1 diabetes. PLoS One 9(2):e89561CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Barker JM, Barriga KJ, Yu L, Miao D, Erlich HA, Norris JM et al (2004) Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). J Clin Endocrinol Metab 89(8):3896–3902CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Juan Martin-Liberal
    • 1
  • Andrew JS Furness
    • 1
    • 2
  • Kroopa Joshi
    • 1
    • 2
  • Karl S. Peggs
    • 2
  • Sergio A. Quezada
    • 2
  • James Larkin
    • 1
    Email author
  1. 1.Renal and Melanoma UnitThe Royal Marsden HospitalLondonUK
  2. 2.Cancer Immunology UnitUniversity College London Cancer InstituteLondonUK

Personalised recommendations