ArticleScience advances2022
Regulation of PD-L1 through direct binding of cholesterol to CRAC motifs.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- DHCR24Oncogene · 2026Article
- Bandgap-Engineered PtAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- Switchable Enzyme-Regulated ECM-Integrin-Cholesterol Signaling Orchestrate PD-L1 Dual Destabilization for Boosting Photo-Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Cholesterol Promotes Lung Adenocarcinoma Brain Metastasis by Stabilizing EGFR Protein to Drive EMT, Metabolic Reprogramming, and Premetastatic Niche Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SREBF2 enhances lipid metabolism and represses anti-tumor immune responses in cervical cancer by increasing ACAT2.Communications biology · 2026Article
- Tumorous cholesterol biosynthesis curtails anti-tumor immunity by preventing MTOR-TFEB-mediated lysosomal degradation of CD274/PD-L1.Autophagy · 2025Article
- Regulatory Mechanisms of Lipid Rafts in Remodeling the Tumor Immune Microenvironment of Colorectal Cancer and Targeted Therapeutic Strategies.Biomolecules · 2025Review
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- Physics-based evolution of transmembrane helices reveals mechanisms of cholesterol attraction.Nature communications · 2025Article
- RPL6 Interacts with HMGCS1 to Stabilize HIF-1α by Promoting Cholesterol Production in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CuOTeDsP nanotherapeutics enhance cuproptosis-mediated immunotherapy by modulating cholesterol metabolism in bladder cancer.Journal of nanobiotechnology · 2025Article
- Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.Nature structural & molecular biology · 2025Article
- Research progress on cholesterol metabolism and tumor therapy.Discover oncology · 2025Review
- Cholesterol-activated stress granules reduce the membrane localization of DRD2 and promote prolactinoma dopamine agonists resistance.Acta neuropathologica communications · 2025Article
- Modulating NPC1L1 to Potentiate PARP Inhibitor-Induced Ferroptosis and Immune Response in Triple-Negative Breast Cancer.Pharmaceutics · 2025Article
- Targeting piRNA-137463 Inhibits Tumor Progression and Boosts Sensitivity to Immune Checkpoint Blockade via De Novo Cholesterol Biosynthesis in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE.Cell death & disease · 2025Article
- Lactylation prognostic signature identifies DHCR7 as a modulator of chemoresistance and immunotherapy efficacy in bladder cancer.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesterol, an essential molecule for cell structure, function, and viability, plays crucial roles in the development, progression, and survival of cancer cells. Earlier studies have shown that cholesterol-lowering drugs can inhibit the high expression of programmed-death ligand 1 (PD-L1) that contributes to immunoevasion in cancer cells. However, the regulatory mechanism of cell surface PD-L1 abundance by cholesterol is still controversial. Here, using nuclear magnetic resonance and biochemical techniques, we demonstrated that cholesterol can directly bind to the transmembrane domain of PD-L1 through two cholesterol-recognition amino acid consensus (CRAC) motifs, forming a sandwich-like architecture and stabilizing PD-L1 to prevent downstream degradation. Mutations at key binding residues prohibit PD-L1-cholesterol interactions, decreasing the cellular abundance of PD-L1. Our results reveal a unique regulatory mechanism that controls the stability of PD-L1 in cancer cells, providing an alternative method to overcome PD-L1-mediated immunoevasion in cancers.
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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.