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Mechanisms Driving Immune-Related Adverse Events in Cancer Patients Treated with Immune Checkpoint Inhibitors

  • Cardio-Oncology (TG Neilan, Section Editor)
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Abstract

Purpose of Review

In the past decade, immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer treatment. With the continuing rise in the number of cancer patients eligible for ICIs, a corresponding rise in immune-related adverse events (irAEs) is occurring. IrAEs are inflammatory reactions against normal, healthy tissue that occur due to ICI-induced activation of the immune system. Although the exact immune pathogenesis driving irAE development remains unknown, we review the main proposed mechanisms, highlighting how they may inform irAE prediction and treatment.

Recent Findings

IrAEs are common and diverse, varying in incidence, timing, and severity. The possible mechanisms driving irAEs include (1) activation of cytotoxic T cells; (2) activation of B cells and increased autoantibody production; (3) direct molecular mimicry and off-target toxicity; (4) activation of intracellular signaling and pro-inflammatory cytokine production; and (5) environmental modifiers of immune system activation, including composition of the host gut microbiome. These mechanisms may help identify predictive biomarkers and targeted treatment strategies.

Summary

IrAEs are driven by multiple components of the immune system. More research is needed to understand their immunopathogenesis so that clinicians across all specialties may more effectively monitor and manage these increasingly common conditions.

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Acknowledgements

The authors thank Robert (Bob) Biedrzycki for working with us to illustrate Fig. 2.

Author information

Authors and Affiliations

  1. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David J. Lee & Howard J. Lee Jr

  2. Allergy and Clinical Immunology Unit, Division of Rheumatology, Allergy & Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jocelyn R. Farmer

  3. Division of Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Kerry L. Reynolds

Authors
  1. David J. Lee
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  2. Howard J. Lee Jr
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  3. Jocelyn R. Farmer
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  4. Kerry L. Reynolds
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Contributions

David Lee, Jocelyn Farmer, and Kerry Reynolds conceived and discussed the idea for the review article. David Lee, Howard Lee, and Kerry Reynolds performed the literature search. David Lee and Howard Lee wrote the manuscript. All authors critically revised the manuscript and approved the final version.

Corresponding author

Correspondence to Kerry L. Reynolds.

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Conflict of Interest

David Lee and Kerry Reynolds have no disclosures to report.

Howard Lee reports working for Immune Design Corporation as an employee from May 2017 to May 2018.

Jocelyn Farmer reports grants from Bristol Myers Squibb and from X4 Pharmaceuticals.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Cardio-Oncology

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Lee, D.J., Lee, H.J., Farmer, J.R. et al. Mechanisms Driving Immune-Related Adverse Events in Cancer Patients Treated with Immune Checkpoint Inhibitors. Curr Cardiol Rep 23, 98 (2021). https://doi.org/10.1007/s11886-021-01530-2

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