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  • Review Article
  • Published:

Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies

This article has been updated

Key Points

  • The emergence of cancer immunotherapy has revolutionized cancer treatment but is associated with serious immune-related adverse effects (IRAEs)

  • Cytotoxic T-lymphocyte antigen 4 (CTLA4)-targeted immunotherapy is associated with increased susceptibility to hypophysitis and primary thyroid dysfunction

  • Programmed cell death protein 1 (PD1)-targeted immunotherapy is associated with primary thyroid dysfunction and type 1 diabetes mellitus

  • CTLA4–PD1 combination therapy has an elevated incidence of hypothyroidism and possibly incidence rates of hypophysitis similar to those with monotherapy with CTLA4 antibodies

  • IRAEs might be associated with improved clinical response of tumours to immunotherapy, but further studies are needed to evaluate this possible effect

Abstract

Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease. In this Review, we describe the current data regarding immune-related endocrinopathies, including hypophysitis, thyroid dysfunction and diabetes mellitus. We discuss the clinical management of these endocrinopathies within the context of our current understanding of the mechanisms of IRAEs.

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Figure 1: Mechanism of action for CTLA4, and PD1 or PDL1 immune checkpoint blockade therapy.
Figure 2: Normal pituitary tissues express ectopic CTLA4 protein.

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Change history

  • 06 February 2017

    In the CTLA4 antibodies section of the above article published online 20 January 2017, 'finding' was misspelled. This has been corrected online.

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D.J.B. and M.G. researched data for the article, made substantial contribution to discussion of the content, wrote, reviewed and edited the manuscript before submission. J.D.W. made substantial contribution to discussion of the content, and reviewed and edited the manuscript before submission. L.M.R. researched data for the article and wrote the manuscript.

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Correspondence to Jedd D. Wolchok or Monica Girotra.

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J.D.W. is a consultant and receives research funding from AstraZeneca, Bristol-Myers Squibb, Genentech, Merck and Medimmune. M.G. has been a consultant for AstraZeneca and Bristol-Myers Squibb. D.J.B. and L.M.R. declare no competing interests.

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Byun, D., Wolchok, J., Rosenberg, L. et al. Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol 13, 195–207 (2017). https://doi.org/10.1038/nrendo.2016.205

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