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Cited by 1,306Hepatocellular Carcinoma Treatment and PrognosisCancer Immunotherapy and BiomarkersHepatitis B Virus Studies

Advances in immunotherapy for hepatocellular carcinoma

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Sangro, Bruno, Sarobe, Pablo, Hervás-Stubbs, Sandra, Melero, Ignacio·2021·Nature Reviews Gastroenterology & Hepatology
DOI 10.1038/s41575-021-00438-0PMC PMC8042636
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Abstract

Hepatocellular carcinoma (HCC) is a prevalent disease with a progression that is modulated by the immune system. Systemic therapy is used in the advanced stage and until 2017 consisted only of antiangiogenic tyrosine kinase inhibitors (TKIs). Immunotherapy with checkpoint inhibitors has shown strong anti-tumour activity in a subset of patients and the combination of the anti-PDL1 antibody atezolizumab and the VEGF-neutralizing antibody bevacizumab has or will soon become the standard of care as a first-line therapy for HCC, whereas the anti-PD1 agents nivolumab and pembrolizumab are used after TKIs in several regions. Other immune strategies such as adoptive T-cell transfer, vaccination or virotherapy have not yet demonstrated consistent clinical activity. Major unmet challenges in HCC checkpoint immunotherapy are the discovery and validation of predictive biomarkers, advancing treatment to earlier stages of the disease, applying the treatment to patients with liver dysfunction and the discovery of more effective combinatorial or sequential approaches. Combinations with other systemic or local treatments are perceived as the most promising opportunities in HCC and some are already under evaluation in large-scale clinical trials. This Review provides up-to-date information on the best use of currently available immunotherapies in HCC and the therapeutic strategies under development. Immunotherapeutic interventions might be effective tools for the treatment of hepatocellular carcinoma. This Review provides up-to-date information on the clinical use of currently available immunotherapies in hepatocellular carcinoma, the mechanisms of response and resistance, and the therapeutic strategies under development.

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  • Combining ICB with anti-angiogenesis therapies has improved efficacy in cancers such as hepatocellular carcinoma (HCC) and biliary tract cancers.

    “Notably, combining ICB with anti-angiogenesis therapies has improved efficacy in cancers such as hepatocellular carcinoma (HCC) and biliary tract cancers.”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [14]

    The Combinations section reports improved survival and progression-free survival in HCC with the checkpoint inhibitor atezolizumab plus the VEGF inhibitor bevacizumab, compared with sorafenib. It does not report improved efficacy for this combination approach in biliary tract cancers; searches for “biliary tract cancers” and “cholangiocarcinoma” found no supporting passage. Page numbers were not available in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Sangro, B., Sarobe, P., Hervás-Stubbs, S., & Melero, I.
Affiliations
  • Clinica Universidad de Navarra (ES)
  • Centro de Investigación Médica Aplicada (ES)
Corresponding author
Sangro, Bruno
ORCID
Venue
Nature Reviews Gastroenterology & Hepatology
Publisher
Springer Science and Business Media LLC
Published
2021-04-13
Volume
18
Issue
8
Pages
525-543
ISSN
  • 1759-5045 (ISSN-L)
  • 1759-5053
DOI
10.1038/s41575-021-00438-0
PMC
PMC8042636
OpenAlex
W3152534107
Cited by
1,306
References
16
Citations by year
2026: 155 · 2025: 215 · 2024: 319 · 2023: 330 · 2022: 232 · 2021: 55
FWCI
31.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Gastroenterology & Hepatology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • European Commission (2014‐2020, HORIZON2020, FEDER 2014-2020, 635122)
  • Gobierno de Navarra
  • Instituto de Salud Carlos III (PI20/00260, PI18/00556, PI19/00742, PI17/00249)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
Keywords
hepatocellular carcinoma, immunotherapy, immune checkpoint inhibitors, PD-1 inhibitors, PD-L1 inhibitors, atezolizumab, bevacizumab, nivolumab, pembrolizumab, tyrosine kinase inhibitors, adoptive T cell therapy, cancer vaccination, virotherapy, predictive biomarkers, immune resistance mechanisms, combination therapy, liver dysfunction
MeSH terms
Carcinoma, Hepatocellular, Humans, Immunotherapy, Liver Neoplasms, Biomarkers, Tumor

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