Blood Adv. 2022 Jul 14:bloodadvances.2022007905. doi: 10.1182/bloodadvances.2022007905. Online ahead of print.
ABSTRACT
Natural Killer (NK) cells are key cells of the innate immune system that share many characteristics with T lymphocytes but whose activation is based on the integration of a range of activatory and inhibitory signals via receptors recognising recurrent pathogen-associated molecular patterns. Two important populations of NK cells with differing functions are recognised; CD56bright and CD56dim. NK cells have the potential to recognise and kill malignant plasma cells, which offers therapeutic opportunities. We used mass cytometry to examine the phenotype and function of NK cell subsets from patients with newly diagnosed multiple myeloma (NDMM). We show that NK cells in NDMM are shifted towards a CD56bright but dysfunctional cytotoxic phenotype which exhibits selective loss of cytokine production. The CD56dim subset has features of exhaustion with impaired proliferation, up-regulation of PD1 and loss of TIM3 expression. Poor expression of NK cell activation markers is seen and is associated with inferior long-term survival. These results suggest that NK cell exhaustion is already present by the time of myeloma diagnosis and likely contributes to the loss of immunological control of malignant plasma cells. Restoring NK cell function via immune directed therapies offers a route to restoring immunological control in multiple myeloma.
PMID:35834731 | DOI:10.1182/bloodadvances.2022007905