Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities

Trends Immunol. 2019 Jun;40(6):511-523. doi: 10.1016/j.it.2019.04.002. Epub 2019 Apr 30.

Abstract

Oncology has recently undergone a revolutionary change with widespread adoption of immunotherapy for many cancers. Immunotherapy using monoclonal antibodies against checkpoint molecules, including programmed death (PD)-1, PD ligand (PD-L)1, and cytotoxic T lymphocyte-associated antigen (CTLA)-4, is effective in a significant subset of patients. However, immune-related adverse events (irAEs) have emerged as frequent complications of checkpoint blockade, likely due to the physiological role of checkpoint pathways in regulating adaptive immunity and preventing autoimmunity. As immunotherapy becomes more common, a better understanding of the etiology of irAEs and ways to limit these events is needed. At the same time, studying these new therapy-related disorders provides an opportunity to better understand naturally occurring human autoimmune and inflammatory disorders, with the potential to improve therapies for cancer and autoimmune diseases.

Keywords: autoimmunity; cancer immunotherapy; checkpoint blockade; immune-related adverse events; tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Autoimmunity
  • Biomarkers, Tumor
  • Disease Management
  • Disease Susceptibility
  • Humans
  • Immunomodulation / drug effects
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Patient Outcome Assessment
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor