Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors

Abstract

SUMMARYEarly immune reconstitution after autologous hematopoietic stem cell transplantation (autoHSCT) is associated with a better outcome in a variety of cancers. NK cells constitute the first lymphocyte subset to recover in the blood after autoHSCT. We have in-depth characterized them in pediatric patients with different tumors and found that, immediately after autoHSCT, NK cells transiently acquired a decidual-like phenotype, were more immature and activated, and exhibited an increased expression of inhibitory receptors, while activating receptors levels were diminished. This activated and decidual-like phenotype was characterized by increased CD56, CD9, CD49a, CD151, CD38, HLA-DR and CD55 expression. We also determined plasma levels of several cytokines and found that their concentrations were associated with the observed changes in NK cells phenotype.In vitroexperiments, including flow cytometry and single-cell RNA sequencing (scRNA-seq), recapitulated the changes observed in NK cells early after autoHSCT. Specifically, results revealed that the combination of IL-15 and TGF-β induced, at least partially, this distinctive phenotype on NK cells after autoHSCT. Finally, we have observed a positive correlation between relapse and the percentage of CD56dimNK cells shortly after autoHSCT in our cohort of pediatric patients. Altogether, our work is of relevance to understand the physiopathology of NK cells during the immune system reconstitution after autoHSCT in children and potentially help in the management of these patients.