Cytokine, cfDNA levels and tumoral DNA profiling in plasma as biomarkers of response to immunotherapy in hepatocellular carcinoma
Background: Immunotherapy has increased the expected survival of patients with advanced HCC. However, objective radiological response to these therapies has been reported to occur in around 20% of patients. Our aim was to identify potential serological markers of response to ICIs. Methods: 25 patients with advanced HCC treated with immunotherapy were prospectively in-cluded. Cytokine and cfDNA/ctDNA levels were measured prior to first treatment administration (basal) and after 3 months of treatment. Basal ctDNA profiling was also analyzed. Results: Basal levels of CTLA-4, cfDNA and ctDNA were significantly different in patients presenting progres-sive disease as best radiological response. The percentage of patients with basal mutations in CDKN2A was significantly higher in patients presenting progressive disease and they have a significantly lower number of CNV. Levels at 3 months of starting the treatment of MCP-1, TNF-alpha, cfDNA and ctDNA were also significantly different between patients with and without progressive disease. Higher cfDNA and ctDNA levels were associated with a poorer overall survival. Conclusion: Analysis of cfDNA and cytokines could help to stratify patients according to expected response to immunotherapies. Overall design: Onco-500 TruSight was performed in basal samples (plasma and whole blood) of 21 patients with HCC treated with immunotherapy.