Supercharged NK cells, unlike primary activated NK cells, effectively target ovarian cancer cells irrespective of MHC-class I expression
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Le résumé fourni par la source
Objective To demonstrate the significance of supercharged natural killer (sNK) cells to target aggressive gynecological tumours. Methods and analysis We used cell cultures of peripheral blood-derived mononuclear cells (PBMCs) and purified NK cells alone and in the presence of tumours. MHC-class gene expression assessments of ovarian tumours were performed using gene set enrichment analysis (GSEA). Secretion and expression levels of cytokines in PBMCs and NK cells were determined using ELISA and scRNA seq analysis, respectively. A flow cytometer was used for surface marker analysis. 51Cr and eSight were used to determine the killing activity of NK cells. Results We have observed a significant decrease in the numbers and functions of NK cells in patients with ovarian cancer. GSEA revealed differently expressed genes, decreased differentiation- and immune-related genes, and increased genes for cell cycle analysis in recurrent tumours compared with chemo-naive ovarian tumours. Increased gene expression as well as secretion of interferon-γ and tumour necrosis factor-α and increased avidity in binding to tumour cells by sNK cells was observed. Unlike primary interleukin (IL)-2-activated NK cells, sNK cells effectively lysed OVCAR8 ovarian poorly differentiated cancer stem-like cells (PDCSCs) and well-differentiated OVCAR4 tumours. Primary ovarian tumours with lower MHC-class I expression were highly susceptible to both primary IL-2-activated NK and sNK cells, whereas the well-differentiated tumours with high expression of MHC-class I were only susceptible to sNK cells. Conclusion The use of sNK cells in immunotherapy emerges as a potentially effective strategy to target and eliminate the majority of ovarian tumour clones, thereby providing a potential therapeutic opportunity in preventing the recurrence of the disease.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Supercharged NK cells, unlike primary activated NK cells, effectively target ovarian cancer cells irrespective of MHC-class I expression
- Date Crossref
- 01/04/2025
- Éditeur
- BMJ
- 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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Hospital Infantil de México Federico Gómez pays non établi dans la noticeÉtablissement de santé
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Oklahoma State University Center for Health Sciences pays non établi dans la noticeÉtablissement de santé
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University of California The Jane and Jerry Weintraub Center for Reconstructive Biotechnology pays non établi dans la noticeUniversité ou école supérieure
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Broad Center pays non établi dans la noticeOrganisation à but non lucratif
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Versiti Blood Center of Wisconsin pays non établi dans la noticeÉtablissement de santé
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Medical College of Wisconsin Department of Microbiology and Immunology pays non établi dans la noticeUniversité ou école supérieure
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Los Angeles Medical Center pays non établi dans la noticeÉtablissement de santé
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Comprehensive Cardiovascular pays non établi dans la noticeÉtablissement de santé
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VA Greater Los Angeles Healthcare System pays non établi dans la noticeÉtablissement de santé
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Oncology Research Unit pays non établi dans la noticeStructure de recherche
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David Geffen School of Medicine Department of Obstetrics and Gynecology pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Molecular Immunology and Immunotherapy pays non établi dans la noticeStructure de recherche
Hospital Infantil de México Federico Gómez, Oklahoma State University Center for Health Sciences et The Jane and Jerry Weintraub Center for Reconstructive Biotechnology — University of California, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.