Cardiorenal complications of immune checkpoint inhibitors

Nat Rev Nephrol. 2018 Sep;14(9):571-588. doi: 10.1038/s41581-018-0035-1.

Abstract

The development of immune checkpoint inhibitors (ICIs) has driven a revolutionary change in cancer treatment. Although traditional chemotherapeutic agents remain the first-line option for most cancers, targeted immune therapies are emerging as standard treatments for advanced-stage cancers. These agents target cell surface checkpoint proteins to stimulate the recognition and destruction of cancer cells by the immune system. Clinical studies have demonstrated these immunotherapeutics to elicit favourable antitumour responses in a variety of chemotherapy-refractory malignancies. However, use of these agents can also induce immune-related adverse events (irAEs) in off-target organs, including the heart and kidney. The most common manifestations of heart and kidney damage are myocarditis and acute interstitial nephritis, respectively, but other manifestations have been reported and, although rare, these off-target effects can be life threatening. Available data suggest that ICIs induce their off-target effects through several mechanisms, including direct binding to cell surface proteins expressed in healthy tissue, activation of T cells that cross-react with off-target tissues, generation of autoantibodies or by increasing levels of pro-inflammatory cytokines. Greater understanding of the adverse effects of cancer immunotherapies and the underlying mechanisms will facilitate the development of biomarkers to identify at-risk patients and approaches to prevent these irAEs.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents, Immunological / adverse effects*
  • B7-H1 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / antagonists & inhibitors
  • Heart Diseases / chemically induced*
  • Heart Diseases / diagnosis
  • Heart Diseases / therapy
  • Humans
  • Ipilimumab / adverse effects*
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / therapy
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Nivolumab / adverse effects*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Signal Transduction / drug effects

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab