Increased Serum Type I Interferon Level May Predict Outcome in Hepatocellular Carcinoma Patients Treated with Radiotherapy

Abstract

Purpose/Objective(s) A growing body of literature indicates that the antitumor response induced by radiotherapy (RT) relies, at least in part, on the activation of Type I Interferon (IFN-I) in cancer, as well as in immune cells. INF-I was the first immunotherapeutic drug approved by the FDA for clinical use in cancer. Here, we investigated 1) whether the blood Interferon-β (IFNβ) level was correlated with the outcomes in patients with hepatocellular carcinoma (HCC) treated with RT, and 2) whether IFNβ expression change after RT in tumor tissue. Materials/Methods In this study, two independent cohorts of patients from a major university hospital were investigated. The main study cohort consisted of 118 patients (77 HBV related) who were enrolled from Feb 2009 to Jan 2018. Blood samples immediately before and 2 weeks after RT were collected prospectively. IFNβ level was measured using an enzyme-linked immunosorbent assay (ELISA). The study endpoints were progression free survival (PFS) and overall survival (OS). The other cohort consisted of 40 HCC patients among whom 20 patients underwent preoperative radiotherapy (Pre-RT) between July 2005 and October 2013, matched with 20 control patients who received surgical resection without RT at same time period. Formalin fixed paraffin embedded tumor tissues of these patients were obtained. IFNβ expression in tumor tissue was evaluated by immunofluorescence and Fiji image analysis software. Results Median IFNβ concentration in pre-treatment HCC patients was 3.5 (range 0.1-10.2) pg/mL and changed heterogeneously and significantly post-treatment to 5.9 (range 0.1-11.4) pg/mL (p < 0.01). On multivariate analysis, post-treatment blood IFNβ level was a significant independent factor for PFS (hazard ratio [HR] 2.408; 95% confidence interval [CI], 1.549–6.877; p = 0.008) and OS (HR 3.019; 95% CI 1.238-7.634; p = 0.012). The patients with increased post-treatment IFNβ level had higher PFS and OS than those without changes or those with reduction in post-treatment levels. In 20 post-irradiated tumor tissue, IFNβ was significantly higher than matched, non-irradiated tissue (p = 0.012). Conclusion High post treatment serum IFNβ levels were associated with better FPS and OS in HCC patients treated with RT. Potentially, IFNβ may be used as noninvasive biomarkers for evaluating HCC malignancy following RT.

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