In vivo expansion of a functionally different CD9 decidual-like NK cell subset following autologous hematopoietic stem cell transplantation

Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. Natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed for the first time RNA-sequencing on NK cells before and after autoHSCT. Results showed profound changes in gene expression profile of NK cells immediately after autoHSCT. Several biological processes including cell cycle, DNA replication and the mevalonate pathway were enriched. Significantly, we observed that following autoHSCT, NK cells acquired a decidual-like gene expression profile. By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, and we observed that these decidual-like NK cells exhibited lower degranulation besides higher granzyme B and perforin expression than CD9- NK cells. These results provide new insights on the physiopathology of NK cells during their reconstitution after autoHSCT. We performed RNA sequencing using RNA from NK cells obtained from blood of Multiple Myeloma patients treated with Autologous Hematopoietic Steam Cell Transplantation (AutoHSCT) at 3 time point (T1 = pre-transplantation; T2 = after recovery of > 1000 leukocytes/ul, around 15 days after transplantation; T3 = 03 days after transplantation).