ArticleCell reports. Medicine2023
Synergistic effects of combined immunotherapy strategies in a model of multifocal hepatocellular carcinoma.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
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- Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137.Oncoimmunology · 2025Article
- Immune checkpoint biology in hepatocellular carcinoma (Review).Oncology letters · 2025Review
- IL7-TBRII, a Dual Cytokine Modulator Targeting IL-7 and TGF-β Pathways, Inhibits Tumor Progression and Metastasis.Immune network · 2025Article
- Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic.Journal for immunotherapy of cancer · 2025Review
- Enhancing HepG2 cell apoptosis with a combined nanoparticle delivery of miR-128-3p agomir and Oroxin B: A novel drug delivery approach based on PI3K-AKT and VEGF pathway crosstalk.Asian journal of pharmaceutical sciences · 2025Article
- Intravital Imaging of Immune Responses in the Cancer Microenvironment.Cancer medicine · 2025Review
- NOTCH1 Drives Sexually Dimorphic Immune Responses in Hepatocellular Carcinoma.Cancer discovery · 2025Article
- Precision models in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025Review
- Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism.Oncoimmunology · 2024Article
- CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects.Science advances · 2023Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint-inhibitor combinations are the best therapeutic option for advanced hepatocellular carcinoma (HCC) patients, but improvements in efficacy are needed to improve response rates. We develop a multifocal HCC model to test immunotherapies by introducing c-myc using hydrodynamic gene transfer along with CRISPR-Cas9-mediated disruption of p53 in mouse hepatocytes. Additionally, induced co-expression of luciferase, EGFP, and the melanosomal antigen gp100 facilitates studies on the underlying immunological mechanisms. We show that treatment of the mice with a combination of anti-CTLA-4 + anti-PD1 mAbs results in partial clearance of the tumor with an improvement in survival. However, the addition of either recombinant IL-2 or an anti-CD137 mAb markedly improves both outcomes in these mice. Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 regimens enhances efficacy in a synergistic manner. As shown by multiplex tissue immunofluorescence and intravital microscopy, combined immunotherapy treatments enhance T cell infiltration and the intratumoral performance of T lymphocytes.
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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.