Related Experiment Video
Updated: Nov 16, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events-A Comprehensive Review
Josefien W Hommes1, Rik J Verheijden2, Karijn P M Suijkerbuijk2
1Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Abstract:
Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of patients with different types of cancer. Through blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), negative feedback mechanisms of the immune system are inhibited, potentially resulting in very durable anti-tumor responses. Despite their promise, ICIs can also elicit auto-immune toxicities. These immune-related adverse events (irAEs) can be severe and sometimes even fatal. Therefore, being able to predict severe irAEs in patients would be of added value in clinical decision making. A search was performed using "adverse events", "immune checkpoint inhibitor", "biomarker", and synonyms in PubMed, yielding 3580 search results. After screening title and abstract on the relevance to the review question, statistical significance of reported potential biomarkers, and evaluation of the remaining full papers, 35 articles were included. Five additional reports were obtained by means of citations and by using the similar article function on PubMed. The current knowledge is presented in comprehensive tables summarizing blood-based, immunogenetic and microbial biomarkers predicting irAEs prior to and during ICI therapy. Until now, no single biomarker has proven to be sufficiently predictive for irAE development. Recommendations for further research on this topic are presented.
Insights
Predicting severe immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) is crucial. Current research, analyzing numerous studies, reveals no single biomarker reliably predicts these potentially fatal toxicities.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1 significantly improve cancer patient outcomes.
- However, ICIs can cause severe immune-related adverse events (irAEs), impacting patient safety.
- Predicting irAEs is vital for clinical decision-making.
Purpose of the Study:
- To comprehensively review and summarize existing biomarkers for predicting irAEs in patients receiving ICIs.
- To identify the predictive value of blood-based, immunogenetic, and microbial markers.
Main Methods:
- A systematic literature search was conducted in PubMed using keywords related to adverse events, ICIs, and biomarkers.
- 35 relevant articles were included after screening, with 5 additional reports identified.
- Data were synthesized into tables summarizing potential predictive biomarkers.
Main Results:
- The review identified various potential biomarkers, including blood-based, immunogenetic, and microbial factors.
- No single biomarker demonstrated sufficient predictive power for irAE development.
- Current predictive models for irAEs remain limited.
Conclusions:
- Despite extensive research, a reliable biomarker for predicting ICI-induced irAEs is yet to be established.
- Further research is recommended to identify robust predictive markers.
- Developing predictive tools for irAEs is essential for optimizing ICI therapy and patient management.
