Natural killer cell-mediated immunosurveillance modulates liver cancer evolution through cancer stemness enhancement and lipid metabolism reprogramming
Rattachement africain : cn, ie. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Tumor evolution enables liver cancer cells to acquire survival advantages and evade therapy-induced cell death. However, the role of natural killer (NK) cells in liver cancer evolution remains unclear. Here, we establish immune-humanized spatiotemporal liver cancer models and integrate single-cell, spatial transcriptomic, and CRISPR/Cas9 screening analyses to investigate this process. We demonstrate that early NK cell-mediated immunosurveillance promotes tumor cell state transition and impairs subsequent adaptive immune responses. Mechanistically, NK cells induce lipid metabolic reprogramming, particularly cholesterol accumulation, and enhance tumor stemness, both of which promote liver cancer evolution. Furthermore, combined anti-LAG-3 treatment and liver X receptor activation suppress tumor evolution and improve the efficacy and durability of immune checkpoint blockade in advanced liver cancer. Collectively, our findings identify that NK cell-mediated early immunosurveillance promotes liver cancer evolution and suggest immunometabolic therapy as a potential strategy for advanced liver cancer. NK cell function in liver cancer has been shown and may influence the progression of liver cancer. Here the authors use mouse liver cancer models and spatial transcriptomics in an immune-humanized liver cancer mouse model to show that NK cells can influence the early progression of liver cancer by altering lipid metabolism and tumour stemness, subsequently demonstrating that inhibition of these pathways can enhance immune cell-mediated tumour control.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Natural killer cell-mediated immunosurveillance modulates liver cancer evolution through cancer stemness enhancement and lipid metabolism reprogramming
- Date Crossref
- 11/06/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Sir Run Run Shaw Hospital pays non établi dans la noticeÉtablissement de santé
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Zhejiang University Department of Orthopaedic Surgery pays non établi dans la noticeUniversité ou école supérieure
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National Instruments (Ireland) pays non établi dans la noticeEntreprise
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Children's Hospital of Zhejiang University pays non établi dans la noticeÉtablissement de santé
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School of Medicine Department of General Surgery pays non établi dans la noticeUniversité ou école supérieure
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National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments pays non établi dans la noticeStructure de recherche
Sir Run Run Shaw Hospital, Department of Orthopaedic Surgery — Zhejiang University et National Instruments (Ireland), avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.