Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function.

Autor:	Carreira-Santos S; Immunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, Spain., López-Sejas N; Immunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, Spain., González-Sánchez M; Immunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, Spain., Sánchez-Hernández E; Immunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, Spain., Pera A; Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain.; Department of Cell Biology, Physiology and Immunology, Universidad de Córdoba, Córdoba, Spain., Hassouneh F; Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain., Durán E; Anatomy and Comparative Pathological Anatomy Unit, Department of Animal Medicine, Faculty of Veterinary Medicine, Universidad de Extremadura, Cáceres, Spain., Solana R; Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain.; Department of Cell Biology, Physiology and Immunology, Universidad de Córdoba, Córdoba, Spain.; Immunology and Allergy Service, Reina Sofia University Hospital, Cordoba, Spain., Casado JG; Immunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, Spain.; Centro de Investigación Biomédica En Red (CIBER) de Enfermedades Cardiovasculares, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.; RICORS-TERAV Network, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.; Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, Cáceres, Spain., Tarazona R; Immunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, Spain.; Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, Cáceres, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Oct 16; Vol. 14, pp. 1256404. Date of Electronic Publication: 2023 Oct 16 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1256404
Abstrakt:	Introduction: Natural killer (NK) cells are a key component of the innate immune system, involved in defending the host against virus-infected cells and tumor immunosurveillance. Under in vitro culture conditions, IL-12/15/18 can induce a memory-like phenotype in NK cells. These cytokine-induced memory-like (CIML) NK cells possess desirable characteristics for immunotherapies, including a longer lifespan and increased cytotoxicity. Methods: In this study, NK cells were isolated from peripheral blood of healthy donors and stimulated with IL-12/15/18 to induce a memory-like phenotype or with IL-15 alone as a control. After seven days of culture, multiparametric flow cytometry analysis was performed to evaluate the phenotypic and functional profiles of CIML and control NK cells. Results: Our results showed a significantly higher expression of CD25, CD69, NKG2D, NKp30, NKp44, NKp46, TACTILE, and Granzyme B in CIML NK cells compared to control NK cells. In contrast, KIR2D expression was significantly lower in CIML NK cells than in control NK cells. Moreover, functional experiments demonstrated that CIML NK cells displayed enhanced degranulation capacity and increased intracellular IFN-γ production against the target cell line K562. Interestingly, the degranulation capacity of CIML NK cells was positively correlated with the expression of the activating receptors NKp46 and NKp30, as well as with the inhibitory receptor TACTILE. Discussion: In conclusion, this study provides a deep phenotypic characterization of in vitro -expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Carreira-Santos, López-Sejas, González-Sánchez, Sánchez-Hernández, Pera, Hassouneh, Durán, Solana, Casado and Tarazona.)
Databáze:	MEDLINE
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