ArticleCancers2019
Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Ashwagandha (Withania somnifera) targets liver cancer stem cells via inhibiting Hedgehog signaling pathway in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Article
- Single-Cell Sequencing and Mendelian Randomization Reveal T Cell Nuclear Factor Genes in Hepatocellular Carcinoma Progression.Human mutation · 2026Article
- Sorafenib-associated Trichodysplasia Spinulosa versus Follicular Hyperkeratosis: a case report.Oxford medical case reports · 2025Article
- Single-cell transcriptomic analysis reveals CD8 + T cell heterogeneity and identifies a prognostic signature in cervical cancer.BMC cancer · 2025Article
- Unravelling infiltrating T-cell heterogeneity in kidney renal clear cell carcinoma: Integrative single-cell and spatial transcriptomic profiling.Journal of cellular and molecular medicine · 2024Article
- Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment.BMC pharmacology & toxicology · 2024Article
- Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer.Cell death & disease · 2024Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Potential use of multikinase inhibitors in immunosuppressed patients with malignancies including thyroid cancer.Cancer medicine · 2022Review
- Review
- Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity.MedComm · 2022Review
- Review
- A novel FBW7/NFAT1 axis regulates cancer immunity in sunitinib-resistant renal cancer by inducing PD-L1 expression.Journal of experimental & clinical cancer research : CR · 2022Article
- A preoperative model based on gadobenate-enhanced MRI for predicting microvascular invasion in hepatocellular carcinomas (≤ 5 cm).Frontiers in oncology · 2022Article
- Novel combinatorial strategies for boosting the efficacy of immune checkpoint inhibitors in advanced breast cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- A phase I trial of sorafenib with whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases and a correlative study of FLT-PET brain imaging.Breast cancer research and treatment · 2021Article
- Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer.World journal of gastrointestinal oncology · 2021Review
- Article
- Kinase inhibitors developed for treatment of hematologic malignancies: implications for immune modulation in COVID-19.Blood advances · 2021Review
- High-Molecular-Weight Fractions of Spruce and Eucalyptus Lignin as a Perspective Nanoparticle-Based Platform for a Therapy Delivery in Liver Cancer.Frontiers in bioengineering and biotechnology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models. In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation. In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials.
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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 Socratic graph.