Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms

Petros Fessas; Lucia A Possamai; James Clark; Ella Daniels; Cathrin Gudd; Benjamin H Mullish; James L Alexander; David J Pinato

doi:10.1111/imm.13141

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.

Authors

Petros Fessas¹, Lucia A Possamai², James Clark¹, Ella Daniels³, Cathrin Gudd², Benjamin H Mullish², James L Alexander², David J Pinato¹

Affiliations

¹ Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
² Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, St Mary's Hospital, London, UK.
³ National Centre for HIV Malignancy, Department of Oncology, Chelsea and Westminster Hospital, London, UK.

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding