NK cell content does not seem to influence engraftment in ex vivo T cell depleted haploidentical stem cell transplantation

We read with great interest the manuscript by Lobo de Figueiredo-Pontes and colleagues (Lobo de Figueiredo-Pontes et al., 2021) on the potential clinical usefulness of NK cellderived IFNg inhibition to favor engraftment in allogeneic hematopoietic stem cell transplantation (HSCT). Indeed, the role of IFNg in regulating hematopoiesis during acute or chronic inflammation through modulation of transcription factor expression and perturbation of cytokine signaling is well characterized (Merli et al., 2021). Thus, we agree that modulation of inflammation of marrow microenvironment may be a useful strategy to favor engraftment in the HSCT setting. We recently confirmed in a clinical setting that IFNg has an important pathogenic role in immunemediated graft failure (GF) (Merli et al., 2019), also showing that inhibition of this cytokine with emapalumab (a clinical grade, IFNg-inhibiting monoclonal antibody developed for the treatment of resistant/relapsed primary HLH; Locatelli et al., 2020) might improve engraftment of selected patients (e.g., those affected by HLH).