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Harnessing Plasma Biomarkers to Predict Immunotherapy Outcomes in Hepatocellular Carcinoma: The Role of cfDNA, ctDNA, and Cytokines

  • 0Liver Cancer Research Group, Liver Diseases, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
International Journal of Molecular Sciences +

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March 27, 2025

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March 27, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Identifying biomarkers like cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) can predict immunotherapy response in advanced hepatocellular carcinoma (HCC). These markers, along with cytokine levels, aid in selecting effective treatments for HCC patients.

Area Of Science

  • Oncology
  • Immunology
  • Genetics

Background

  • Immunotherapy offers survival benefits for advanced hepatocellular carcinoma (HCC) but shows variable response rates.
  • Objective radiological responses to immune checkpoint inhibitors (ICIs) are observed in only about 20% of HCC patients.
  • Predictive biomarkers are needed to optimize ICI treatment selection in HCC.

Purpose Of The Study

  • To identify serologic markers that predict radiological response to ICIs in advanced HCC.
  • To investigate the association of cfDNA, ctDNA, and cytokine levels with treatment outcomes.
  • To explore the role of genomic profiling, including gene mutations and copy number variations (CNVs), in predicting HCC response to immunotherapy.

Main Methods

  • Prospective analysis of 38 advanced HCC patients receiving immunotherapy.
  • Measurement of cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and cytokine levels pre-treatment and three months post-treatment.
  • Genomic profiling of ctDNA, including mutation analysis (e.g., CDKN2A) and assessment of CNVs.

Main Results

  • Baseline cfDNA and ctDNA levels differentiated HCC patients based on radiological response to ICIs.
  • Pathologic mutations in the CDKN2A gene were associated with significantly reduced survival.
  • Patients with progressive disease (PD) showed fewer CNVs compared to responders.
  • Post-treatment levels of IL10, PD1, and TGFβ correlated with survival status.

Conclusions

  • Serologic markers including cfDNA and ctDNA show promise in predicting response to ICIs in advanced HCC.
  • Genomic alterations like CDKN2A mutations and CNVs may influence survival outcomes.
  • Cytokine profiling after three months of treatment can provide further prognostic information.
  • Analysis of cfDNA, ctDNA, and cytokines can potentially improve treatment selection for HCC patients undergoing immunotherapy.

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