ArticleOncotarget2017
Atorvastatin downregulates co-inhibitory receptor expression by targeting Ras-activated mTOR signalling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses 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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Concomitant Statins and the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Meta-Analysis.International journal of clinical practice · 2022Pooled it
- Pooled it
- Effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in people living with HIV with dyslipidemia and receiving ritonavir-boosted atazanavir: a randomized, double-blind, crossover study.AIDS research and therapy · 2023Trial
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Survival and response outcomes in patients with recurrent/metastatic head and neck cancer treated with opioids and statins: an exploratory pilot study.Translational cancer research · 2026Article
- Dietary ω-3 polyunsaturated fatty acids (PUFAs) reduce cholesterol-driven non-small cell lung cancer (NSCLC) progression in mouse models of disease.Communications medicine · 2025Article
- Polyfunctional CD8Molecular oncology · 2025Article
- Impact of rosuvastatin on the memory potential and functionality of CD8EBioMedicine · 2025Article
- Enhancing the Efficacy of CAR-T Cell Production Using BX795 and Rosuvastatin in a Serum-Free Medium.International journal of molecular sciences · 2025Article
- Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer.Cancer medicine · 2025Article
- Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma.Journal of translational medicine · 2025Article
- Mechanisms and implications of vascular-homing CD8 T cells in atherosclerosis.NPJ cardiovascular health · 2025Review
- Strategies to Overcome PD-1/PD-L1 Blockade Resistance: Focusing on Combination with Immune Checkpoint Blockades.Journal of Cancer · 2025Review
- Cholesterol and Immune Microenvironment: Path Towards Tumorigenesis.Current nutrition reports · 2024Review
- Immunometabolism: a new dimension in immunotherapy resistance.Frontiers of medicine · 2023Review
- Decoding the crosstalk between mevalonate metabolism and T cell function.Immunological reviews · 2023Review
- Statin drugs enhance responses to immune checkpoint blockade in head and neck cancer models.Journal for immunotherapy of cancer · 2023Article
- Atorvastatin Enhances the Efficacy of Immune Checkpoint Therapy and Suppresses the Cellular and Extracellular Vesicle PD-L1.Pharmaceutics · 2022Article
- Identification of a New Cholesterol-Binding Site within the IFN-γ Receptor that is Required for Signal Transduction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The cholesterol pathway: impact on immunity and cancer.Trends in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulation of T cell function in the steady state is mediated by co-inhibitory receptors or immune checkpoints such as PD-1, CTLA-4, TIM-3 and LAG-3. Persistent antigen stimulation, during chronic viral infections and cancer, results in sustained expression of multiple co-inhibitory receptors and subsequently poor effector T cell function. Immune checkpoint blockade using monoclonal antibodies against PD-1, PDL-1 and CTLA-4 has been implemented as an immunotherapy strategy- resulting in restoration of T cell function and reduction of viral load or tumour growth. Immunomodulatory roles of commonly used cholesterol-lowering medications, atorvastatin and other statins, are widely documented. We have previously shown that atorvastatin can inhibit HIV-1 infection and replication. Here, for the very first time we discovered that atorvastatin also regulates activated T cell function by mediating downregulation of multiple co-inhibitory receptors, which corresponded with increased IL-2 production by stimulated T cells. In addition, we found that atorvastatin treatment reduces expression of mTOR and downstream T cell effector genes. We demonstrate a novel mechanism showing that atorvastatin inhibition of Ras-activated MAPK and PI3K-Akt pathways, and subsequent mTOR signalling promotes gross downregulation of co-inhibitory receptors. Thus, our results suggest that statins may hold particular promise in reinvigorating T cell function in chronic conditions.
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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.