ArticleOncotarget2015
Amphiregulin activates regulatory T lymphocytes and suppresses CD8+ T cell-mediated anti-tumor response in hepatocellular carcinoma cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Pooled it
- Regulatory T Cell Heterogeneity in the Steady State and Tumor.Immune network · 2026Review
- Genetic diversity of Collaborative Cross mice implicates FFAR3 as a target for ILC2 anti-inflammatory reprogramming.Nature communications · 2026Article
- Sensitizing Immune-Refractory Ovarian Tumors via p53 Mutation-Tailored Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma.Head & face medicine · 2024Article
- Enhanced amphiregulin exposure promotes modulation of the high grade serous ovarian cancer tumor immune microenvironment.Frontiers in pharmacology · 2024Article
- Short-chain fatty acids in cancer pathogenesis.Cancer metastasis reviews · 2023Review
- PRR11 is a prognostic biomarker and correlates with immune infiltrates in bladder urothelial carcinoma.Scientific reports · 2023Article
- Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma.Frontiers in immunology · 2023Review
- The Role of Immune Modulatory Cytokines in the Tumor Microenvironments of Head and Neck Squamous Cell Carcinomas.Cancers · 2022Review
- Immunosuppressive tumor microenvironment modulation by chemotherapies and targeted therapies to enhance immunotherapy effectiveness.Oncoimmunology · 2022Review
- Advances in Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma.Frontiers in immunology · 2022Review
- TNFSF9 Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Pancreatic Cancer.Journal of gastrointestinal cancer · 2021Article
- The Combination Immunotherapy of TLR9 Agonist and OX40 Agonist via Intratumoural Injection for Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2021Article
- FOXP3 expression in FOXP3Translational cancer research · 2020Article
- Amphiregulin Aggravates GlomerulonephritisJournal of the American Society of Nephrology : JASN · 2020Article
- "Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.Frontiers in oncology · 2020Review
- Innate lymphoid cell composition associates with COVID-19 disease severity.Clinical & translational immunology · 2020Article
- High Blood miR-802 Is Associated With Poor Prognosis in HCC Patients by Regulating DNA Damage Response 1 (REDD1)-Mediated Function of T Cells.Oncology research · 2019Article
- From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD8+ T cell-mediated immune response plays an important role in inhibiting progression of hepatocellular carcinoma (HCC). For strategic immunotherapy, it is critical to understand why some of the tumor cells escape from this immune attack. In this study, we investigated how HCC cells alter endogenous anti-tumor immunity and their related signaling pathways. We found that HCC cells, both in vitro and in vivo, substantially secret and express amphiregulin (AR). AR in turn activates immunosuppressive function of intratumoral CD4+Foxp3+ regulatory T cells (Tregs), a major inhibitor of CD8+ T cells. Using either lentiviral siRNA, or AR neutralizing antibody, we blocked the expression and function of AR to test the specificity of AR mediated activation of Tregs, Biochemical and cell biology studies were followed and confirmed that blocking of AR inhibited Tregs activation. In addition, we found that AR can trigger the activation of rapamycin complex 1(mTORC1) signaling in Tregs. The mTORC1 inhibitor rapamycin treatment led to compromise Treg function and resulted in enhancing anti-tumor function of CD8+ T cells. Blocking AR/EGFR signaling in Tregs with Gefitinib also enhanced anti-tumor immunity and decreased tumor size in a mouse xenograft tumor model. Taken together, our study suggested a novel mechanism of functional interaction between HCC and Tregs for regulating anti-tumor function of CD8+ T cells.
Indexed as
Identifiers
What OpenQuestion holds
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.