Myeloma cells induce the accumulation of activated CD94low NK cells by cell-to-cell contacts involving CD56 molecules

Chiara Barberi, Claudia de Pasquale, Alessandro Allegra, Giacomo Sidoti Migliore, Daniela Oliveri, Fabrizio Loiacono, Vanessa Innao, Caterina Musolino, Daniela Pende, Claudia Cantoni, Paolo Carrega, Maria Cristina Mingari, Stefania Campana, Guido Ferlazzo

Research output: Contribution to journalArticlepeer-review

Abstract

Natural killer (NK) cells represent innate effector cells potentially able to play a role during the immune response against multiple myeloma (MM). To better define the distribution and the specific properties of NK cell subsets during MM disease, we analyzed their features in the bone marrow and peripheral blood of newly diagnosed MM patients. Our findings revealed that, in both compartments, NK cells were more abundant than in healthy donors. Among total MM-NK cells, a significant increase of CD94lowCD56dim NK cell subset was observed, which already appears in clinical precursor conditions leading to MM, namely monoclonal gammopathy of undetermined significance and smoldering MM, and eventually accumulates with disease progression. Moreover, a consistent fraction of CD94lowCD56dim NK cells was in a proliferation phase. When analyzed for their killing abilities, they represented the main cytotoxic NK cell subset against autologous MM cells. In vitro, MM cells could rapidly induce the expansion of the CD94lowCD56dim NK cell subset, thus reminiscent of that observed in MM patients. Mechanistically, this accumulation relied on cell to cell contacts between MM and NK cells and required both activation via DNAM-1 and homophilic interaction with CD56 expressed on MM cells. Considering the growing variety of combination treatments aimed at enhancing NK cell-mediated cytotoxicity against MM, these results may also be informative for optimizing current immunotherapeutic approaches.

Original languageEnglish
Pages (from-to)2297-2307
Number of pages11
JournalBlood advances
Volume4
Issue number10
DOIs
Publication statusPublished - May 26 2020

ASJC Scopus subject areas

  • Hematology

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