improvement of nk cell cytotoxicity in reconstituting nk cells after allogeneic stem cell transplantation by blocking nkg2a checkpoint

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.