ArticleESMO open2026
Peripheral blood DNA methylation profile and immune checkpoint inhibitor response in cancer patients.
Article in ESMO open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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19 authors.
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Abstract
backgroundEpigenome-wide association studies of blood DNA methylation have linked epigenetic changes to immune-related mechanisms. In oncology, DNA methylation profiling holds promise as a predictive biomarker. We aimed to evaluate peripheral blood DNA methylation profiles as a potential biomarker for predicting immune checkpoint inhibitor (ICI) response. PATIENTS AND
methodsPatients with advanced solid tumors who received palliative ICI treatment were prospectively enrolled. DNA methylation profiling was performed on peripheral blood specimens using Infinium MethylationEPIC BeadChip (Illumina Inc., San Diego, CA). Baseline and longitudinal samples were collected. Treatment response was evaluated using the iRECIST guidelines by a board-certified radiologist.
resultsA total of 274 peripheral blood samples from 233 patients (median age, 64 years; female, 35.6%; male, 64.4%) were analyzed (214 baseline, 41 matched baseline and follow-up samples; overlapping cohorts). Blood methylation profiles at baseline were used to distinguish responders from nonresponders, with differentially methylated CpG sites enriched in immune-related and tumor-associated pathways. Blood methylation profile differences were independent of immune cell composition and count as well as sex and entity, suggesting cell-intrinsic epigenetic features. In longitudinal samples from 41 patients with metastatic lung cancer, responders exhibited significant therapy-associated methylation changes, whereas no changes in the blood methylation profile were observed in the nonresponders.
conclusionsOur findings demonstrate that the blood-based DNA methylation profile correlates with the response to ICI therapy across solid cancer entities. Changes during treatment reflect the dynamic immune remodeling induced by the ICI response. Overall, blood-based DNA methylation profiles might serve as tumor-agnostic patient-specific biomarkers.
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