ArticleFrontiers in immunology2025
Cholesterol metabolism shapes immune low-response states in LUAD: a multi-omics cholesterol metabolism signature predicts immunotherapy benefit and identifies DHCR7 as a therapeutic target.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Immunometabolic editing of the tumor microenvironment: from reprogramming mechanisms to therapeutic vulnerabilities.Frontiers in immunology · 2025Review
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6 authors.
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Abstract
Background: Cholesterol metabolism has been shown to affect the tumor microenvironment in various cancers, but its immunological role in lung adenocarcinoma (LUAD) remains unclear. Methods: We integrated 1,682 LUAD samples (including 7 treatment-naïve bulk cohorts and 3 immunotherapy bulk cohorts) to develop a Cholesterol Metabolism Signature (CMS) based on cholesterol metabolism-associated genes. Survival analysis, ROC curves, and PCA were used to evaluate the ability of CMS to predict prognosis and immunotherapy efficacy. Immune infiltration analysis, single-cell transcriptomics, as well as Results: CMS effectively predicted the survival outcomes and immunotherapy benefits of LUAD patients, which was consistently validated in all independent cohorts. Patients with high CMS had worse prognosis. Compared with 51 previously published LUAD signatures, CMS showed higher predictive accuracy and stratification ability. Immune-related analyses showed that the high CMS group had reduced immune cell infiltration and suppressed immune function, which was further supported by single-cell analysis revealing enhanced immunosuppressive pathways. Expression of the key gene DHCR7 was highly correlated with CMS score (R = 0.42, P<0.05), negatively associated with many immune-related genes and immune cycles, and promoted poor prognosis and cancer pathways. Multiplex immunohistochemistry confirmed that regions with high DHCR7 expression had fewer infiltrating CD8T and CD20B cells. Conclusion: Our study demonstrates that the CMS can effectively predict prognosis and immunotherapy response in LUAD. DHCR7, as a key gene in CMS, is closely related to immune suppression and poor prognosis. Inhibition of DHCR7 can improve the tumor immune microenvironment and enhance the efficacy of immunotherapy, suggesting that DHCR7 is a potential new target for LUAD immunotherapy.
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