Ricerc@Sapienza

Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance
of multiple myeloma (MM) since they are able to directly recognize
and kill MM cells. In this regard, among activating receptors expressed by NK cells,
NKG2D represents an important receptor for the recognition of MM cells, being its
ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The
MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded

Treatment of multiple myeloma (MM) cells with sub-lethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 up-regulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells (PCs) from patients' bone marrow (BM) aspirates.