Biomarkers for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors
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Yao Liang1, Osamu Maeda1, Yuichi Ando1
1Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi, Japan.
Abstract:
Although immune checkpoint inhibitors have greatly improved cancer therapy, they also cause immune-related adverse events, including a wide range of inflammatory side effects resulting from excessive immune activation. Types of immune-related adverse events are diverse and can occur in almost any organ, with different frequencies and severities. Furthermore, immune-related adverse events may occur within the first few weeks after treatment or even several months after treatment discontinuation. Predictive biomarkers include blood cell counts and cell surface markers, serum proteins, autoantibodies, cytokines/chemokines, germline genetic variations and gene expression profiles, human leukocyte antigen genotype, microRNAs and the gut microbiome. Given the inconsistencies in research results and limited practical utility, there is to date no established biomarker that can be used in routine clinical practice, and additional investigations are essential to demonstrate efficacy and subsequently facilitate integration into routine clinical use.
Insights
Immune checkpoint inhibitors improve cancer treatment but can cause diverse immune-related adverse events. Currently, no reliable biomarkers exist for predicting these events in clinical practice, necessitating further research.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy.
- However, ICIs can induce immune-related adverse events (irAEs), characterized by excessive immune activation and inflammation.
- irAEs manifest diversely across organs, with varying onset and severity, impacting patient treatment.
Purpose of the Study:
- To review the landscape of potential predictive biomarkers for immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy.
- To highlight the challenges and limitations in current biomarker research for irAEs.
- To emphasize the need for further investigation to enable clinical integration of predictive biomarkers.
Main Methods:
- Comprehensive literature review of studies investigating biomarkers for irAEs.
- Analysis of various biomarker categories including blood cell counts, autoantibodies, cytokines, genetic variations, and the gut microbiome.
- Evaluation of the current status and clinical utility of identified biomarkers.
Main Results:
- A wide array of potential predictive biomarkers have been explored, including cell surface markers, serum proteins, autoantibodies, cytokines, genetic variations, and the gut microbiome.
- Despite extensive research, significant inconsistencies in results and limited practical utility hinder the establishment of reliable predictive biomarkers.
- No single biomarker or combination thereof is currently validated for routine clinical use in predicting irAEs.
Conclusions:
- The development of validated predictive biomarkers for immune-related adverse events remains a critical unmet need in cancer immunotherapy.
- Current research highlights numerous candidate biomarkers, but further rigorous investigation is essential to establish their efficacy and clinical utility.
- Successful integration of predictive biomarkers into routine clinical practice requires robust validation studies to ensure reliable patient management and treatment optimization.
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