摘要:SummaryNatural killer (NK) cells are usually identified by the absence of other lineage markers, due to the lack of cell-surface-specific receptors. CD56negNK cells, classically identified as CD56negCD16+, are very scarce in the peripheral blood of healthy people but they expand in some pathological conditions. However, studies on CD56negNK cells had revealed different results regarding the phenotype and functionality. This could be due to, among others, the unstable expression of CD16, which hinders CD56negNK cells’ proper identification. Hence, we aim to determine an alternative surface marker to CD16 to better identify CD56negNK cells. We have found that NKp80 is superior to CD16. Furthermore, we found differences between the functionality of CD56negNKp80+ and CD56negCD16+, suggesting that the effector functions of CD56negNK cells are not as diminished as previously thought. We proposed NKp80 as a noteworthy marker to identify and accurately re-characterize human CD56negNK cells.Graphical AbstractDisplay OmittedHighlights•NKp80 is a more precise marker than CD16 in order to identify CD56negNK cells•CD16, but no NKp80, is downmodulated after cryopreservation and cell activation•CD56negNK cells effector functions are not as diminished as previously describedBiological Sciences; Immunology