Young Eun Chon, Ju Hyun Shim, Joo Hyun Oh, Jiwon Yang, Hyunjae Shin, Wonseok Kang, Yeongseok Hwang, Su Jong Yu, Jongman Kim, Hae Won Lee, Yoon Jun Kim, Sook-Hyang Jeong
Clin Mol Hepatol 2025;31(4):1107-1114. Published online October 1, 2025
Adjuvant cytokine-induced killer cell immunotherapy in hepatocellular carcinoma: real-world data and 9-year extended follow-up of a randomized controlled trial Hyunjae Shin, Youngsu Park, Byeong Geun Song, Won-Mook Choi, Hyung Joon Han, Youngwoo Lee, Tae-Jin Song, Jong-Eun Yeon, Young-Suk Lim, Moon Haeng Hur, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Joon Hyeok Lee, Jung-Hwan Yoon, Jeong-Hoon Lee Cancer Immunology, Immunotherapy.2026;[Epub] CrossRef
Background/Aims The abscopal effect, a rare phenomenon induced by radiation, can be reinforced by immunotherapy. Although radiation therapy and immunotherapy are increasingly being utilized for the treatment of hepatocellular carcinoma (HCC), whether immunotherapy could boost the abscopal effect remains unclear. In this study, we aimed to elucidate the immunological mechanisms underlying the abscopal effect induced by the combination of irradiation and immunotherapy in a murine HCC model.
Methods A syngeneic HCC mouse model was established by transplanting murine Hepa 1–6 HCC cells into both hind legs of immunocompetent C57BL/6 mice. The tumors on the right hind legs were irradiated, and abscopal effects were observed in the non-irradiated tumors on the left hind leg with or without the coadministration of anti-programmed cell death 1 (PD-1) antibodies. Flow cytometric analyses were performed to analyze the distributions of immune cells infiltrating both irradiated and non-irradiated tumors and the tumor-draining lymph nodes (TDLNs).
Result s: Administration of 16 Gy in two fractions more effectively inhibited the growth of both irradiated and nonirradiated tumors with higher tumor infiltration of cytotoxic T cells than 8 Gy did in a single fraction. The higher dose also increased activated dendritic cells in TDLNs, which had higher expression of the programmed cell death ligand 1. Coadministration of anti-PD-1 antibodies significantly enhanced the abscopal effect and increased infiltration of activated cytotoxic T cells in both irradiated and non-irradiated tumors.
Conclusions Our findings show that adding anti-PD-1 therapy to radiation enhanced the abscopal effect in a syngeneic murine model of HCC.
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Background/Aims Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown.
Methods A total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed.
Result s: During a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years.
Conclusions The HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.
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Background/Aims We investigated the outcomes of early-stage hepatocellular carcinoma (HCC) patients who showed a complete response (CR) to initial transarterial chemoembolization (TACE), with a focus on the role of scheduled TACE repetition.
Methods A total of 178 patients with early-stage HCC who were initially treated with TACE and showed a CR based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria on one month follow-up computed tomography (CT) were analyzed. Among them, 90 patients underwent scheduled repetition of TACE in the absence of viable tumor on CT.
Result s: During a median follow-up period of 4.6 years (range: 0.4-8.8 years), mortality was observed in 71 patients (39.9%). The overall recurrence-free and local recurrence-free survival rates at 1 year were 44.4% and 56.2%. In the multivariable model, scheduled repetition of TACE was an independent factor associated with survival (hazard ratio [95% confidence interval]: 0.56 [0.34-0.93], P=0.025). When stratified using Barcelona clinic liver cancer (BCLC) stage, scheduled repetition of TACE was associated with a favorable survival rate in BCLC stage A patients, but not in BCLC 0 patients.
Conclusions Scheduled repetition of TACE was associated with better survival for early-stage HCC patients showing a CR after initial TACE, especially in BCLC stage A patients.
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