ArticleThe Journal of clinical investigation2023
Combination of AFP vaccine and immune checkpoint inhibitors slows hepatocellular carcinoma progression in preclinical models.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 37 citations in OpenAlex.
- Personalized immunotherapy in HCC: synthesis, delivery, and clinical progress of mRNA-based vaccines.Cancer cell international · 2026Review
- Precise regulation of cancer vaccine and immune checkpoint inhibitor synergy potentiates immunotherapy with reduced immune-related pneumonitis.Materials today. Bio · 2026Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- Immune-modified exosome vaccine loaded with liver cancer epitope peptides induces potent and specific antitumor immunity.Journal of nanobiotechnology · 2026Article
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Site-specific neoepitope induction by RNA editing reprograms tumor immunogenicity.Frontiers in immunology · 2026Article
- TSIX: A Novel Long Noncoding RNA in Cancer Development and Progression.Current pharmaceutical design · 2026Review
- ScRNA-Seq Deciphers an Autocrine EFNA1-EPHA1 Loop That Reprograms the Microenvironment in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Mechanisms of Immune Checkpoint Inhibitor Resistance in Hepatocellular Carcinoma and Strategies for Reversal.Cancers · 2025Review
- Inhibition of GSK3 and TSC2 Mediates the Oncogenic Activity of AKT in Hepatocellular Carcinoma.Cancer research · 2025Article
- GPC3-based circular RNA vaccine suppresses hepatocellular carcinoma progression by activating adaptive immune responses.Hepatology (Baltimore, Md.) · 2025Article
- The Roles and Clinical Significance of Major Hepatic-Derived Metabolites in Hepatocellular Carcinoma.Journal of gastroenterology and hepatology · 2025Review
- Alpha fetoprotein (AFP)-producing gastric cancer: clinicopathological features and treatment strategies.Cell & bioscience · 2025Review
- Exploring the Multifunctional Role of Alpha-Fetoprotein in Cancer Progression: Implications for Targeted Therapy in Hepatocellular Carcinoma and Beyond.International journal of molecular sciences · 2025Review
- Improving immunotherapy for the treatment of hepatocellular carcinoma: learning from patients and preclinical models.Gut and liver · 2025Review
- Dual mRNA nanoparticles strategy for enhanced pancreatic cancer treatment and β-elemene combination therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Review
- Advances in Tumor Microenvironment and Immunotherapeutic Strategies for Hepatocellular Carcinoma.Oncology research · 2025Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
Abstract
Many patients with hepatocellular carcinoma (HCC) do not respond to the first-line immune checkpoint inhibitor treatment. Immunization with effective cancer vaccines is an attractive alternative approach to immunotherapy. However, its efficacy remains insufficiently evaluated in preclinical studies. Here, we investigated HCC-associated self/tumor antigen, α-fetoprotein-based (AFP-based) vaccine immunization for treating AFP (+) HCC mouse models. We found that AFP immunization effectively induced AFP-specific CD8+ T cells in vivo. However, these CD8+ T cells expressed exhaustion markers, including PD1, LAG3, and Tim3. Furthermore, the AFP vaccine effectively prevented c-MYC/Mcl1 HCC initiation when administered before tumor formation, while it was ineffective against full-blown c-MYC/Mcl1 tumors. Similarly, anti-PD1 and anti-PD-L1 monotherapy showed no efficacy in this murine HCC model. In striking contrast, AFP immunization combined with anti-PD-L1 treatment triggered significant inhibition of HCC progression in most liver tumor nodules, while in combination with anti-PD1, it induced slower tumor progression. Mechanistically, we demonstrated that HCC-intrinsic PD-L1 expression was the primary target of anti-PD-L1 in this combination therapy. Notably, the combination therapy had a similar therapeutic effect in the cMet/β-catenin mouse HCC model. These findings suggest that combining the AFP vaccine and immune checkpoint inhibitors may be effective for AFP (+) HCC treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.