NK Cell Immaturity and NKp30 Expression Positively Correlate with Clinical Outcome in Multiple Myeloma Patients from the IFM2009 Clinical Trial

Multiple myeloma (MM) is a proliferation of tumoral plasma cells that is still incurable. Natural killer (NK) cells can recognize and kill MM cells in vitro. However, previous literature suggests an alteration of NK cell function in MM patients. To further evaluate this point, we used multi-parametric flow cytometry to monitor NK cell phenotype in bone marrow samples at diagnosis of MM, taking advantage of the IFM2009 trial and associated samples. Our results show an increase in the frequency of NK cells in MM patients. A detailed analysis of NK cell phenotype showed a decreased expression of terminal maturation markers such as KLRG1 or CD57 and an increased expression of CD56^bright/tissue resident markers among NK cells from MM patients. The extent of these alterations is even more pronounced as the ISS score increases in patients. Finally, a favorable clinical evolution correlates with NK cell immaturity, on the one hand, and with the level of NKp30, a receptor more expressed in immature NK cells on the other hand. Altogether, these data suggest that immature and resident NK cells are particularly involved in the anti-myeloma response, notably via NKp30, which could pave the way for future therapeutic strategies.