ArticleEMBO molecular medicine2024
Shaping immune landscape of colorectal cancer by cholesterol metabolites.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 18 citations in OpenAlex.
- Cancer-associated fibroblasts drive immune resistance in MSS colorectal cancer via the FAIM2-CES1-ER stress pathway.Molecular and cellular biochemistry · 2026Article
- Cholesterol as a metabolic integrator of oncogenic signaling, immune evasion, and therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Inflammation and Colorectal Cancer Pathogenesis: Molecular, Immunological, and Environmental Features for Therapy Response and Resistances.International journal of molecular sciences · 2026Review
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Key immune cells in the tumor immune microenvironment of colorectal cancer: Roles and research advances (Review).Oncology reports · 2026Review
- Palmitic acid activates c-Myc via dual palmitoylation-dependent pathways to promote colon cancer.Cell discovery · 2026Article
- Pan-cancer analysis of cholesterol metabolism reveals the uptake as a modulator of tumor immune features and of the KRAS pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- 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
- Multi-omics analysis reveals different cholesterol metabolism subtypes in colorectal cancer.Discover oncology · 2025Article
- Dysregulated Cholesterol Metabolism and Its Impact on the Tumour Immune Response in Colorectal Cancer.Journal of cellular and molecular medicine · 2025Review
- CYP51A1 in health and disease: from sterol metabolism to regulated cell death.Cell death discovery · 2025Review
- S-adenosylmethionine metabolism shapes CD8Cancer & metabolism · 2025Article
- Naples Prognostic Score (NPS) as a Novel Prognostic Score for Stage III Breast Cancer Patients: A Real-World Retrospective Study.Breast cancer (Dove Medical Press) · 2025Article
- Cholesterol effects on the tumor immune microenvironment: from fundamental concepts to mechanisms and implications.Frontiers in oncology · 2025Review
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Editorial: Reviews and advances in the molecular mechanisms of breast cancer.Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
28 authors at 8 institutions in 1 country.
Funding
Abstract
Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.
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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.