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Characterize local and systemic cytokine changes due to transarterial chemoembolization and their relation to treatment response and overall survival in hepatocellular carcinoma.

May 7, 2026Theranostics0 citationsOpen Access

Local and systemic cytokine signatures for outcome prediction after transarterial chemoembolization in hepatocellular carcinoma

EYEmine Y. YilmazMax Delbrück Center RSRobin SchmidtMax Delbrück Center LHLuisa HeidemannMax Delbrück Center

Key Points

Characterize local and systemic cytokine changes due to transarterial chemoembolization and their relation to treatment response and overall survival in hepatocellular carcinoma.
Prospective single-center study involving 46 patients with unresectable hepatocellular carcinoma
Blood and tumor interstitial fluid samples collected before treatment and post-cTACE
Cytokine levels measured with multiplex assays and correlated with radiologic responses and survival outcomes.
Post-cTACE cytokine changes included significant decreases in serum IFN-, MCP-1, TNF-, IL-8, and IL-4, with an increase in IL-6 (p < 0.005)
Responders in the iBT group had elevated TIF IL-8 (p = 0.0103) prior to treatment; responders in the cTACE/iBT group exhibited lower TIF bFGF post-cTACE (p = 0.0449)
Elevated baseline serum IL-6 and IL-8 were linked to shorter overall survival, while higher TIF IFN- correlated with improved survival.

Abstract

Purpose: Conventional transarterial chemoembolization (cTACE) is a guideline-approved therapy for unresectable hepatocellular carcinoma (HCC).This study aimed to characterize systemic and local cytokine changes induced by cTACE, and to evaluate their correlation with treatment response, Lipiodol deposition, and overall survival (OS).Experimental Design: In this prospective single-center study, 46 patients with unresectable HCC underwent either cTACE followed by interstitial brachytherapy (iBT) after 24h (n = 23) or iBT alone (n = 23).Peripheral blood samples were obtained before treatment in both groups and 24h post-cTACE in the cTACE/iBT group.Additionally, tumor interstitial fluid (TIF) was isolated from tumor biopsies that were collected prior to iBT from untreated tumors (iBT group) or 24h post-cTACE (cTACE/iBT group).Serum and TIF cytokines were quantified using multiplex assays and correlated with radiologic response at 8-week MRI, Lipiodol patterns on CT 24h post-cTACE, and OS.Results: Post-cTACE, serum IFN-, MCP-1, TNF-, MIP-1, IL-17, IL-8, IL-4, and IL-5 significantly decreased, while IL-6 increased (p < 0.005).TIF analysis showed higher IL-17 in untreated tumors compared to post-cTACE (p = 0.038), but differences were modest.In the iBT group, responders had elevated TIF IL-8 (p = 0.0103) and VEGF-A (p = 0.0185) prior to treatment, whereas in the cTACE/iBT group, responders exhibited lower TIF bFGF post-cTACE than non-responders (p = 0.0449).Elevated baseline serum IL-6 (p = 0.052), IL-8 (p = 0.036), and IFN- (p = 0.0508) were associated with shorter OS, while higher TIF IFN- (p = 0.051) correlated with improved OS. Baseline serum IL-1 (p = 0.0266) and post-cTACE serum level of VEGF-A (p = 0.0318) were higher in patients with homogeneous Lipiodol deposition in tumors, which correlated with longer OS.Conclusions: cTACE induces distinct systemic and local immune alterations that influence patient outcomes.Specifically, elevated serum IL-6 predicted poor survival, while homogeneous Lipiodol deposition marks favorable immune modulation and outcomes.Combining cytokine profiling with imaging biomarkers may enable improved, personalized treatment strategies in HCC.

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