Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S. Lee, Ahmed O. Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A. Curran, Ji Hoon Kim, Ju-Seog Lee
Clin Mol Hepatol 2025;31(2):669-670. Published online February 27, 2025
Reply to correspondence on “Genomic biomarkers to predict response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma: Insights from the IMbrave150 trial” Hiroaki Kanzaki, Yujin Hoshida Clinical and Molecular Hepatology.2025; 31(1): e121. CrossRef
Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S. Lee, Ahmed O. Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A. Curran, Ji Hoon Kim, Ju-Seog Lee
Clin Mol Hepatol 2024;30(4):807-823. Published online July 23, 2024
Background/Aims Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.
Methods Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab.
Results The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of antitumor macrophages and activated T-cells, potentially explaining its better response.
Conclusions Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.
Citations
Citations to this article as recorded by
Targeting TIME in advanced hepatocellular carcinoma: Mechanisms of drug resistance and treatment strategies Xinyi Ye, Xizhu Fang, Fangfang Li, Dan Jin Critical Reviews in Oncology/Hematology.2025; 211: 104735. CrossRef
Differential Infiltration of T-Cell Populations in Tumor and Liver Tissues Predicts Recurrence-Free Survival in Surgically Resected Hepatocellular Carcinoma Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung Cancers.2025; 17(9): 1548. CrossRef
Advances in cancer immunotherapy: historical perspectives, current developments, and future directions Meiyin Zhang, Chaojun Liu, Jing Tu, Min Tang, Milad Ashrafizadeh, Noushin Nabavi, Gautam Sethi, Peiqing Zhao, Shijian Liu Molecular Cancer.2025;[Epub] CrossRef
Management and Outcomes of Adverse Events Following Immune Checkpoint Inhibitor Treatment in Patients with Hepatocellular Carcinoma Soon Kyu Lee, Bo Hyun Kim Journal of Digestive Cancer Research.2025; 13(1): 65. CrossRef
Managing hepatocellular carcinoma recurrence after liver transplantation: emerging role of immune checkpoint inhibitors Mohammad Saeid Rezaee-Zavareh, Soo Young Hwang, Naomy Kim, Hasmik Adetyan, Nguyen H. Tran, Ju Dong Yang Discover Oncology.2025;[Epub] CrossRef
Hepatic Metabolic Signature and Its Association with the Response to Immunotherapy in Hepatocellular Carcinoma Hyewon Park, Sowon Park, Kena Park, Sun Young Yim, Ju-Seog Lee, Sung Hwan Lee ImmunoTargets and Therapy.2025; Volume 14: 787. CrossRef
Development and validation of a risk prediction model for patients with hepatocellular carcinoma receiving atezolizumab–bevacizumab Heechul Nam, Dong Yun Kim, Do Young Kim, Ji Hoon Kim, Chang Wook Kim, Jaejun Lee, Keungmo Yang, Ji Won Han, Pil Soo Sung, Seung Kew Yoon, Hee Sun Cho, Hyun Yang, Si Hyun Bae, Soon Kyu Lee, Jung Hyun Kwon, Soon Woo Nam, Ahlim Lee, Do Seon Song, U Im Chang, Hepatology.2025;[Epub] CrossRef
Bulk and Single-Cell Transcriptomes Reveal Exhausted Signature in Prognosis of Hepatocellular Carcinoma Ruixin Chun, Haisen Ni, Ziyi Zhao, Chunlong Zhang Genes.2025; 16(9): 1034. CrossRef
Efficacy and Safety of Different Doses of Bevacizumab Combined with Atezolizumab in Unresectable Hepatocellular Carcinoma Shaobo Zhang, Jiabei Wang, Zebin Zhu, Peng Ji, Yanli Wang, Kun Cheng, Björn Nashan, Lianxin Liu, Shugeng Zhang Journal of Hepatocellular Carcinoma.2025; Volume 12: 2007. CrossRef
Ultrasounic-radiomics models for predicting the response to Atezolizumab plus Bevacizumab in patients with unresectable hepatocellular carcinoma Yiran Li, Zonghan Liu, Yi Qian, Kang Wang, Yijun Gu, Yan Chen, Haozheng Jiang, Shuqun Cheng, Dong Jiang, Xinjun Lu PLOS One.2025; 20(10): e0334099. CrossRef
Prognostic Significance of Glypican-3 Expression in Hepatocellular Carcinoma Treated with Atezolizumab-Bevacizumab Ji Hoon Kim, Ji Won Han, Hee Sun Cho, Jeong Won Jang, Kwon Yong Tak, Pil Soo Sung Cancers.2025; 17(24): 3967. CrossRef
An Early Increase in IL-10 and TNF-α Levels Following Atezolizumab Plus Bevacizumab Treatment Predicts Survival in Advanced Hepatocellular Carcinoma Patients: A Prospective Cohort Study Soon Kyu Lee, Soon Woo Nam, Ji Won Han, Jung Hyun Kwon Cancers.2024; 16(20): 3543. CrossRef
From biomarker discovery to combined therapies: Advancing hepatocellular carcinoma treatment strategies Mo-Wei Kong, Yang Yu, Ying Wan, Yu Gao, Chun-Xiang Zhang World Journal of Gastrointestinal Oncology.2024; 16(11): 4518. CrossRef
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