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Improvement of NK Cell Cytotoxicity in Reconstituting NK Cells after Allogeneic Stem Cell Transplantation by Blocking NKG2A Checkpoint

Document Type : Original Article(s)

Authors

1 Department of Pharmacology and Medical Sciences, Faculty of Pharmacy, Al-Azhar University of Gaza, Gaza, Palestine

2 Cancer Research Center of Marseille (CRCM), CNRS, Faculty of Medicine, Aix Marseille University, Marseille, France

Abstract

Background: One cause of tumor relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the alteration of the graft-versus-tumor effect of early reconstituting natural killer (NK) cells due to overexpression of the NKG2A inhibitory receptor. This study aims to determine the effect of Monalizumab, an anti- NKG2A receptor, on the effector functions of reconstituting NK cells after allo-HSCT.
Method: In this prospective cohort study, 18 patients with hematological malignancies were divided into three groups: dose 1 group (0.1 mg/kg, n = 5), dose 2 group (0.5 mg/kg, n = 8), and dose 3 group (1 mg/kg, n = 5), and followed up for six months. Blood samples were taken directly before the administration of Monalizumab and at different time points post-treatment. Reconstituting NK cells were phenotypically and functionally assessed by flow cytometry.
Results: Our results showed a more pronounced increase in the expression of activating NK receptors (NKG2D, NKp30, NKp46) on the reconstituting CD56dim NK cells of patients receiving 1 mg/kg of Monalizumab compared with other participants. Additionally, we observed that patients treated with dose 3 of Monalizumab had the highest levels of degranulation compared with other patients and controls. Moreover, we noticed that CD56dim NK cells of dose 2- and dose 3-related patients produced significant levels of perforin, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) in response to K562 stimulation post-Monalizumab treatment compared with controls and dose 1-treated patients.
Conclusion: We suggest that using Monalizumab improves the phenotype and cytotoxicity of reconstituting NK cells after allo-HSCT.

Keywords

Main Subjects

How to cite this article:

Taha M, Fauriat C. Improvement of NK cell cytotoxicity in reconstituting NK cells after allogeneic stem cell transplantation by blocking NKG2A checkpoint. Middle East J Cancer. 2023;14(4):509-20. doi:10.30476/mejc.2023.97716.1876.

 

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Middle East Journal of Cancer
Volume 14, Issue 4 - Serial Number 56
October 2023
Pages 509-520
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