NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27

Alessandra Dondero, Beatrice Casu, Francesca Bellora, Angelo Vacca, Annunziata De Luisi, Maria Antonia Frassanito, Claudia Cantoni, Silvia Gaggero, Daniel Olive, Alessandro Moretta, Cristina Bottino, Roberta Castriconi

Research output: Contribution to journalArticlepeer-review


Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM), a still incurable malignancy. Here we analyzed the activity of cytokine-stimulated NK cells against tumor-associated endothelial cells isolated from bone marrow aspirates of MM patients with active disease (MMECs). We show that NK cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted action of multiple activating receptors. In particular, according to the high expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target recognition. Interestingly, in MMECs the surface density of PVR was significantly higher than that detected in endothelium from patients with MM in complete remission or with monoclonal gammopathy of undetermined significance (MGUS). Importantly, IL-27, which unlike IL-15 does not display pro-angiogenic properties, maintained or increased the NK cell functions induced by suboptimal concentrations of IL-15. NK cell properties included killing of MMECs, IFN-γ production as well as a peculiar increase of NKp46 expression on NK cell surface. Finally, IL-27 showed a striking capability of up-regulating the expression of PD-L2 and HLA-I on tumor endothelium, whereas it did not modify that of PD-L1 and HLA-II.Our results suggest that cytokine-activated endogenous or adoptively transferred NK cells might support conventional therapies improving the outcome of MM patients.

Original languageEnglish
Pages (from-to)35088-35102
Number of pages15
Issue number21
Publication statusPublished - May 23 2017


  • Journal Article


Dive into the research topics of 'NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27'. Together they form a unique fingerprint.

Cite this