Journal Article

Adjuvant cytokine-induced killer cell immunotherapy in hepatocellular carcinoma: real-world data and 9-year extended follow-up of a randomized controlled trial

Lee, Joon Hyeok, Lim, Young-Suk, Hur, Moon Haeng, Yu, Su Jong, Song, Tae-Jin, Song, Byeong Geun, Yeon, Jong-Eun, Kim, Yoon Jun, Yoon, Jung-Hwan, Lee, Yun Bin, Park, Youngsu, Cho, Eun Ju, Lee, Jeong-Hoon, Lee, Youngwoo, Han, Hyung Joon, Shin, Hyunjae, Choi, Won-Mook

2026

Overview

Background Most adjuvant therapies for hepatocellular carcinoma (HCC) have failed except for autologous cytokine-induced killer (CIK) therapy, which prolonged recurrence-free survival (RFS) in a previously reported randomized controlled trial (RCT) and real-world data (RWD). Methods This study aimed to assess the long-term outcomes of adjuvant CIK therapy using both an extended follow-up of the original RCT and a retrospective cohort study. An extended follow-up analysis of the RCT included 226 patients (114 in the CIK group and 112 in the control group). The follow-up duration was extended from 2 to 9 years after the enrollment of the last patient. In parallel, a retrospective RWD study was performed involving 577 patients from two tertiary centers in Korea, including 251 who received adjuvant CIK therapy and 326 controls. Propensity score matching (PSM) was applied to adjust for baseline imbalances. The primary endpoint was RFS in both studies. Results In the RWD study (median follow-up = 57.2 months), the CIK group demonstrated significantly prolonged RFS than controls both before PSM (median = 101.2 versus 64.7 months; HR = 0.69, 95% CI 0.53–0.90, P  = 0.006) and after PSM (median = 101.2 vs. 65.7 months; HR = 0.64, 95% CI 0.45–0.91, P  = 0.01). In the extended follow-up of the RCT (median follow-up = 116.1 months), the CIK group exhibited significantly prolonged RFS (median = 44.0 vs. 30.0 months; hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.54–0.97, P  = 0.033) compared to the control group. Conclusions Adjuvant CIK cell therapy significantly improved RFS in both a RWD study and a 9-year extended RCT follow-up, supporting its reproducible benefit in reducing recurrence after curative treatment of HCC. These consistent findings provide strong evidence for the clinical utility of CIK therapy as a durable adjuvant immunotherapeutic strategy for HCC.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V,Springer
• Subject: Adjuvant immunotherapy / Adult / Aged / Cancer Research / Carcinoma, Hepatocellular - immunology / Carcinoma, Hepatocellular - mortality / Carcinoma, Hepatocellular - therapy / Cell therapy / Clinical trials / Cytokine-induced killer cells / Cytokine-Induced Killer Cells - immunology / Cytokine-Induced Killer Cells - transplantation / Cytokines / Female / Follow-Up Studies / Hepatitis B / Hepatitis C / Hepatocellular carcinoma / Humans / Immune system / Immunology / Immunotherapy / Immunotherapy - methods / Immunotherapy, Adoptive - methods / Infections / Liver cancer / Liver cirrhosis / Liver diseases / Liver Neoplasms - immunology / Liver Neoplasms - mortality / Liver Neoplasms - therapy / Magnetic resonance imaging / Male / Medical prognosis / Medical records / Medicine / Medicine & Public Health / Middle Aged / Oncology / Patients / Real-world evidence / Recurrence-free survival / Retrospective Studies / Treatment Outcome / Tumors