Impending HCC diagnosis in patients with cirrhosis after HCV cure features a natural killer cell signature
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Le résumé fourni par la source
BACKGROUND AND AIMS: The risk of developing HCC in chronically infected patients with AQ2 HCV with liver cirrhosis is significantly elevated. This risk remains high even after a sustained virological response with direct-acting antivirals. To date, disease-associated signatures of NK cells indicating HCC development are unclear. APPROACH AND RESULTS: This study investigated NK cell signatures and functions in 8 cohorts covering the time span of HCC development, diagnosis, and onset. In-depth analysis of NK cell profiles from patients with cirrhosis who developed HCC (HCV-HCC) after sustained virological response compared with those who remained tumor-free (HCV-noHCC) revealed increasingly dissimilar NK cell signatures over time. We identified expression patterns with persistently high frequencies of TIM-3 and CD38 on NK cells that were largely absent in healthy controls and were associated with a high probability of HCC development. Functional assays revealed that the NK cells had potent cytotoxic features. In contrast to HCV-HCC, the signature of HCV-noHCC converged with the signature found in healthy controls over time. Regarding tissue distribution, single-cell sequencing showed high frequencies of these cells in liver tissue and the invasive margin but markedly lower frequencies in tumors. CONCLUSIONS: We show that HCV-related HCC development has profound effects on the imprint of NK cells. Persistent co-expression of TIM-3hi and CD38 + on NK cells is an early indicator for HCV-related HCC development. We propose that the profiling of NK cells may be a rapid and valuable tool to assess the risk of HCC development in a timely manner in patients with cirrhosis after HCV cure.
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
- Impending HCC diagnosis in patients with cirrhosis after HCV cure features a natural killer cell signature
- Date Crossref
- 20/02/2024
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- 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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Medizinische Hochschule Hannover pays non établi dans la noticeUniversité ou école supérieure
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Karolinska University Hospital Department of Medicine Huddinge pays non établi dans la noticeÉtablissement de santé
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Karolinska Institutet pays non établi dans la noticeUniversité ou école supérieure
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German Center for Infection Research pays non établi dans la noticeStructure de recherche
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Centre for Individualised Infection Medicine pays non établi dans la noticeStructure de recherche
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Department of Gastroenterology pays non établi dans la noticeInstitution
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ZIB program pays non établi dans la noticeInstitution
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Centre for Individualized Infection Medicine (CIIM) pays non établi dans la noticeInstitution
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Cluster of Excellence RESIST pays non établi dans la noticeInstitution
Medizinische Hochschule Hannover, Department of Medicine Huddinge — Karolinska University Hospital et Karolinska Institutet, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.