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

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

• natural killer cells
• monalizumab
• nkg2a
• cell cytotoxicity
• allogeneic hematopoietic stem cell transplantation