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Immune mechanisms of toxicity from checkpoint inhibitors

S Jennifer Wang1, Stephanie K Dougan2, Michael Dougan3

  • 1Department of Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.

Trends in Cancer
|April 28, 2023
PubMed

Insights

Immune checkpoint inhibitors (ICIs) offer durable cancer remission but can cause severe toxicities. This review details ICI-related toxicities and proposes optimized management strategies to balance treatment efficacy and patient safety.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Cancer immunotherapy has advanced significantly with immune checkpoint inhibitors (ICIs).
  • ICIs targeting CTLA-4, PD-1, and PD-L1 induce durable remissions in metastatic cancers.
  • However, ICIs can cause severe, potentially life-threatening inflammatory toxicities across organ systems.

Purpose of the Study:

  • To review the current understanding of inflammatory toxicities associated with ICIs.
  • To discuss the mechanisms driving these toxicities.
  • To propose optimal treatment strategies for managing ICI-induced toxicities.

Main Methods:

  • Review of existing literature on immune checkpoint inhibitor toxicities.
  • Analysis of molecular and cellular mechanisms underlying ICI-related adverse events.
  • Synthesis of current management approaches and future research directions.

Main Results:

  • Significant progress has been made in understanding ICI toxicity drivers.
  • Effective management strategies for these toxicities have been developed.
  • Further research is needed to predict and optimize therapies for ICI toxicities.

Conclusions:

  • ICI therapy offers substantial benefits but carries risks of inflammatory toxicities.
  • Understanding toxicity mechanisms is crucial for developing safer and more effective treatments.
  • Optimized strategies are needed to manage toxicities without compromising antitumor immunity.
Keywords:
cancer immunotherapycheckpoint blockadeimmune checkpoint inhibitorimmune-related adverse eventsinflammatory toxicity

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