[PDF][PDF] Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors
NG Nunez, F Berner, E Friebel, S Unger, N Wyss… - Med, 2023 - cell.com
NG Nunez, F Berner, E Friebel, S Unger, N Wyss, JM Gomez, MT Purde, R Niederer…
Med, 2023•cell.comSummary 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 …
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 …
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.
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