Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms

Immunology. 2020 Feb;159(2):167-177. doi: 10.1111/imm.13141. Epub 2019 Nov 19.

Abstract

Immune checkpoint inhibition with monoclonal antibodies is becoming increasingly commonplace in cancer medicine, having contributed to a widening of therapeutic options across oncological indications. Disruption of immune tolerance is the key mechanism of action of checkpoint inhibitors and although immune-related adverse events are a typical class effect of these compounds, the relationship between toxicity and response is not fully understood. Awareness and vigilance are paramount in recognizing potentially life-threatening toxicities and managing them in a timely manner. In this review article, we provide an overview of the clinical features, pathological findings and management principles of common immune-related toxicities, attempting to provide mechanistic insight into an increasingly common complication of cancer therapy.

Keywords: immune checkpoint inhibitors; immunotherapy; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / adverse effects*
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / therapy
  • Endocrine System Diseases / chemically induced*
  • Endocrine System Diseases / immunology
  • Endocrine System Diseases / metabolism
  • Endocrine System Diseases / therapy
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / immunology
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / therapy
  • Humans
  • Immune Tolerance / drug effects*
  • Immunotherapy / adverse effects*
  • Lung Diseases / chemically induced*
  • Lung Diseases / immunology
  • Lung Diseases / metabolism
  • Lung Diseases / therapy
  • Molecular Targeted Therapy / adverse effects*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Risk Factors
  • Tumor Escape / drug effects

Substances

  • Antineoplastic Agents, Immunological