ArticleFrontiers in immunology2025
Low rather than high interleukin-6 levels are associated with immune-related adverse events in cancer patients treated with immune checkpoint inhibitors.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Dynamic peripheral immune monitoring during checkpoint blockade: a framework for interpreting response, toxicity and resistance.Frontiers in immunology · 2026Review
- Peripheral blood biomarkers in PD-1/PD-L1 immunotherapy: distinguishing predictive from prognostic biomarkers.Frontiers in immunology · 2026Review
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11 authors.
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Abstract
Background: Among the biomarkers associated with immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) in cancer patients, interleukin-6 (IL-6) has emerged as a key predictive factor. However, it remains unclear whether high or low levels of IL-6 predispose patients to irAEs. Our objective was to evaluate the strength of the association between circulating IL-6 levels, measured in cancer patients before and after initiating ICIs, and the risk of irAEs. Methods: In this multicenter, prospective pan-cancer cohort study, serum IL-6 levels were quantified immediately before the first (pre-ICI) and second (post-ICI) cycles of ICI therapy. To assess the association between IL-6 and irAEs, Fine and Gray competing risk regression models were fitted, considering irAEs as the main event and death as the competing event. The incremental predictive value of IL-6 levels was evaluated using Harrell's C-index. Results: Overall, 224 patients were followed up for a median of 75.5 days after ICI initiation. The adjusted 1-year cumulative incidence of irAEs was 49.0% (95% confidence interval [95%CI], 41.9-55.6%). Multivariate regression models identified female sex (hazard ratio [HR], 1.81; 95%CI, 1.17-2.81; p=0.008), dual ICI therapy with nivolumab plus ipilimumab (HR, 1.86; 95%CI, 1.14-3.02; p=0.012) and post-ICI IL-6 levels (HR, 0.97; 95%CI, 0.94-1.00; p=0.049) as independent risk factors for irAEs. Using standardized post-ICI IL-6 levels, the effect was stronger, with an HR of 0.74 (95% CI, 0.55-1.00; p=0.049). Adding post-ICI IL-6 levels to a model containing established irAE risk factors improved the Harrell's C-index from 0.623 to 0.640. Conclusion: In cancer patients treated with ICIs, low rather than high post-ICI IL-6 levels, female sex and dual ICI therapy are independent risk factors for irAEs.
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