Faculty, Staff and Student Publications

Publication Date

10-1-2024

Journal

Clinical and Molecular Hepatology

DOI

10.3350/cmh.2024.0333

PMID

39038962

PMCID

PMC11540371

PubMedCentral® Posted Date

7-23-2024

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Conclusion: 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.

Keywords

Humans, Carcinoma, Hepatocellular, Bevacizumab, Liver Neoplasms, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Male, Sorafenib, Female, Immunotherapy, Middle Aged, Aged, Nivolumab, Hepatocellular carcinoma, Immunotherapy, Atezolizumab, Bevacizumab, Transcriptome

Comments

This article has been corrected. See Clin Mol Hepatol. 2025 Feb 27.

Published Open-Access

yes

Additional Files
cmh-2024-0333e.pdf (1848 kB)
Correction
cmh-2024-0333f8.jpg (113 kB)
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