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Circulating Transcriptome Analysis Finds Gene Signatures and Immune Cell Activation and Abundance Predict Response to
Sandy Chevrier1, Corentin Richard1, Olivier Adotévi2,3
1Université Bourgogne Europe, Georges-François Leclerc Cancer Center, UNICANCER, Unit of Molecular Biology, Department of Biology and Pathology of Cancer, ICMUB UMR CNRS 6302, Dijon, France.
Whole blood RNA sequencing can predict patient responses to immune checkpoint blockers (ICB) and identify potential side effects. This blood test may improve cancer treatment efficacy and management of immune-related adverse events (irAEs).
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immune checkpoint blockers (ICB) offer durable responses in advanced cancers.
- Current biomarkers (PD-L1, MSI, TMB) have limitations in predicting ICB efficacy.
- Novel biomarkers are needed to optimize patient selection and treatment management.
Purpose of the Study:
- To evaluate the utility of whole blood RNA sequencing for predicting response to ICB.
- To identify gene expression signatures associated with clinical benefit and survival.
- To explore the association of blood-based biomarkers with immune-related adverse events (irAEs).
Main Methods:
- Prospective enrollment of 164 patients in the IOPREDI study.
- Paired-end total RNA sequencing of baseline whole blood samples.
- Analysis of differential gene expression, pathway activation, and immune cell abundance.
Main Results:
- Immune-related genes and pathways were highly expressed in patients with durable clinical benefit.
- Higher expression of immune pathways correlated with improved progression-free survival (PFS) and overall survival (OS).
- Resting NK cell abundance predicted longer PFS/OS, while CST7 gene expression and naive B cells indicated irAE risk.
Conclusions:
- Whole blood RNA sequencing provides robust data for predicting ICB response, survival, and irAEs.
- Pre-treatment blood RNA sequencing can enhance treatment efficacy and irAE management.
- This approach offers a promising tool for personalized immunotherapy strategies.
