The DOI matches its Crossref record; 205 of the 205 references it cites were found in a registry or an index.
Biomarkers for immunotherapy of hepatocellular carcinoma
Abstract
Immune-checkpoint inhibitors (ICIs) are now widely used for the treatment of patients with advanced-stage hepatocellular carcinoma (HCC). Two different ICI-containing regimens, atezolizumab plus bevacizumab and tremelimumab plus durvalumab, are now approved standard-of-care first-line therapies in this setting. However, and despite substantial improvements in survival outcomes relative to sorafenib, most patients with advanced-stage HCC do not derive durable benefit from these regimens. Advances in genome sequencing including the use of single-cell RNA sequencing (both of tumour material and blood samples), as well as immune cell identification strategies and other techniques such as radiomics and analysis of the microbiota, have created considerable potential for the identification of novel predictive biomarkers enabling the accurate selection of patients who are most likely to derive benefit from ICIs. In this Review, we summarize data on the immunology of HCC and the outcomes in patients receiving ICIs for the treatment of this disease. We then provide an overview of current biomarker use and developments in the past 5 years, including gene signatures, circulating tumour cells, high-dimensional flow cytometry, single-cell RNA sequencing as well as approaches involving the microbiome, radiomics and clinical markers. Novel concepts for further biomarker development in HCC are then discussed including biomarker-driven trials, spatial transcriptomics and integrated 'big data' analysis approaches. These concepts all have the potential to better identify patients who are most likely to benefit from ICIs and to promote the development of new treatment approaches.
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“Currently, there are no validated predictive biomarkers for patient response to immunotherapy in HCC100.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [100]
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Items 201–205 of 205
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Research works printed but not linked: 2
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Antiangiogenic–immune-checkpoint inhibitor combinations: lessons from phase III clinical trials
Kuo, H., Khan, K. A., & Kerbel, R. S. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00886-y · Cited by 140
Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy
Seyhan, D., Allaire, M., Fu, Y., Conti, F., Wang, X. W., Gao, B., & Lafdil, F. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01308-4 · Cited by 138
Self-citationExtracellular Vesicles for Clinical Diagnostics: From Bulk Measurements to Single-Vesicle Analysis
Tran, H. L., Zheng, W., Issadore, D., Im, H., Cho, Y., Zhang, Y., Liu, D., Liu, Y., Li, B., Liu, F., et al. (2025) · ACS Nano · doi:10.1021/acsnano.5c00706 · Cited by 117
Cancer stem cells and niches: challenges in immunotherapy resistance
Pan, Y., Yuan, C., Zeng, C., Sun, C., Xia, L., Wang, G., Chen, X., Zhang, B., Liu, J., & Ding, Z. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02265-2 · Cited by 117
Le, J., Dian, Y., Zhao, D., Guo, Z., Luo, Z., Chen, X., Zeng, F., & Deng, G. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02426-3 · Cited by 118
Metadata
- Authors
- Greten, T. F., Villanueva, A., Korangy, F., Ruf, B., Yarchoan, M., Ma, L., Ruppin, E., & Wang, X. W.
- Affiliations
- National Institutes of Health (US)
- Tisch Cancer Institute (US)
- National Cancer Institute (US)
- Johns Hopkins University (US)
- Corresponding author
- Greten, Tim F.
- ORCID
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2023-09-19
- Volume
- 20
- Issue
- 11
- Pages
- 780-798
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W4386845699
- Cited by
- 227
- References
- 205
- Citations by year
- 2026: 66 · 2025: 88 · 2024: 71 · 2023: 2
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hepatocellular carcinoma, immune checkpoint inhibitors, predictive biomarkers, atezolizumab plus bevacizumab, single-cell RNA sequencing, circulating tumor cells, high-dimensional flow cytometry, tumor microbiome, radiomics, gene expression signatures, spatial transcriptomics, biomarker-driven trials, immunotherapy selection
- MeSH terms
- Sorafenib, Carcinoma, Hepatocellular, Humans, Immunotherapy, Liver Neoplasms, Biomarkers
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