한빛사논문
- 조회150
Sun Young Yim1, Sung Hwan Lee2, Seung-Woo Baek3, Bohwa Sohn4, Yun Seong Jeong4, Sang-Hee Kang5, Kena Park6,7, Hyewon Park4, Sunyoung S. Lee8, Ahmed O. Kaseb8, Young Nyun Park9, Sun-Hee Leem10,11, Michael A. Curran12, Ji Hoon Kim1, Ju-Seog Lee4
1Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
2Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, CHA Bundang Medical Center, CHA University, Korea
3Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea
4Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
5Department of Surgery, Korea University Guro Hospital, Seoul, Korea
6Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea
7Department of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
8Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
9Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
10Department of Biomedical Sciences, Dong-A University, Busan 49315, Republic of Korea
11Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea
12Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
*Sun Young Yim and Sung Hwan Lee contributed equally to this work.
Correspondence : Ju-Seog Lee
Abstract
Introduction: 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 anti-tumor 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.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-07-24)
- 국내+국외 연구진
- 의약학 > 종양의학
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