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Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint
Nicolas Gonzalo Nuñez1, Fiamma Berner2, Ekaterina Friebel1
1Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Background:
Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs.
Methods:
In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs.
Findings:
When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs.
Conclusions:
We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs.
Funding:
This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen.
Insights
Predicting immune-related adverse events (irAEs) from immune checkpoint inhibitor (ICI) therapy is crucial. Early increases in specific cytokines and T cells in patient blood can indicate a heightened risk of irAEs.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) offer promising cancer treatments for melanoma and NSCLC.
- However, ICIs can cause severe immune-related adverse events (irAEs).
- Predictive biomarkers for irAEs are needed for risk-benefit analysis and understanding treatment mechanisms.
Purpose of the Study:
- To identify biomarkers predicting irAEs in patients receiving ICIs.
- To characterize the systemic immune response during ICI therapy using multi-omics.
Main Methods:
- Prospective multi-center study.
- Combined multi-omics: single-cell PBMC profiling and serum proteomics.
- Analyzed over 300 PBMC and 500 serum samples.
Main Results:
- Identified potential predictive biomarkers for irAEs by integrating multi-omics data.
- Early increases in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) within 1-2 weeks predict irAE risk.
- Early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells associated with increased irAE risk.
Conclusions:
- A combination of cellular and proteomic biomarkers can predict irAE risk.
- These biomarkers may help identify patients benefiting most from ICI therapy.
- Aids in selecting patients needing intensive irAE monitoring.
