Abstract
Natural Killer (NK) cells play a pivotal role in the immunosurveillance of Multiple Myeloma (MM), but it is still undefined whether the NK cell functional properties underlying their protective activity against MM are confined to distinct NK cell populations. Interestingly, herein we report that the CD56lowCD16low NK cell subset displayed higher cytolytic activity compared to the other NK cell subsets (i.e., CD56highCD16+/−, CD56lowCD16high) against MM cells and its activity was impaired in MM patients. Decreased DNAM-1 expression levels were observed on the CD56lowCD16low NK cells during MM progression. Evaluating NK cell subset frequency after autologous hematopoietic stem cell transplantation, we found that CD56lowCD16low NK cells recovered earlier after transplantation. Overall, our data denote a key role of CD56lowCD16low subpopulation in the killing of MM cells and suggest that the reconstitution of CD56lowCD16low subpopulation after HSCT could be a useful approach of adoptive immunotherapy in the treatment of relapsed/refractory MM patients.
Highlights
Natural Killer (NK) cells are innate immune effector lymphocytes with a pivotal role in the immune response against cancer cells
The usage of anti-SLAMF7/CD319 monoclonal antibody elotuzumab exerts its anti-MM activity mainly via NK cell-mediated antibody dependent cellular cytotoxicity (ADCC) through the CD16 receptor and the triggering of CD319/SLAMF7 on NK cells [13,14]. It is still undefined whether the functional properties underlying NK cell protective activity against MM are confined to distinct NK
bone marrow (BM) CD56low CD16low NK Cells from MM Patients Show a Decreased Expression of DNAM-1 and NKp30. To phenotypically characterize both total NK cells and NK cell subsets in MM patients, we evaluated the expression levels of three different activating NK cell receptors namely NKG2D, DNAM-1 (CD226) and NKp30 involved in the recognition and killing of MM
Summary
Natural Killer (NK) cells are innate immune effector lymphocytes with a pivotal role in the immune response against cancer cells. NK cell killing of cancer cells depends on the integration of intracellular signaling cascades initiated by the engagement of different cell-surface inhibitory and activating receptors [1]. Multiple myeloma (MM) is a clonal B cell malignancy characterized by expansion of plasma cells (PCs) in the bone marrow (BM) [2]. At present, it is still an incurable disease with a median survival not exceeding five years, and its prognosis has been recently meliorated by the use of autologous hematopoietic stem cell transplantation (HSCT) and by new immunochemotherapeutic approaches [3,4]. Among the activating receptors expressed by NK cells, NKG2D, DNAM-1
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