Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies

Nat Rev Endocrinol. 2017 Apr;13(4):195-207. doi: 10.1038/nrendo.2016.205. Epub 2017 Jan 20.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • CTLA-4 Antigen / biosynthesis
  • Endocrine System Diseases / chemically induced*
  • Endocrine System Diseases / immunology*
  • Endocrine System Diseases / metabolism
  • Humans
  • Immunotherapy / adverse effects
  • Ipilimumab
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Programmed Cell Death 1 Receptor / biosynthesis

Substances

  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor