Clinical stage-depending decrease of NK cell activity in multiple myeloma patients

Abstract

Natural killer cells, as an important subpopulation of cells of the innate immune system have an essential role in defense of the rise and spread of malignancy. These cells have a CD3-CD16 + CD56+ phenotype and they are functionally defined by their ability to lyses tumor cells. We here show that decrease of NK cell activity was significantly associated with advanced clinical stage, increased lactate dehydrogenase (LDH), percentage infiltration of bone marrow with plasma cells, and beta-2 microglobulin. The patients with higher NK cell activity at presentation after receiving VAD protocol have better cumulative survival in comparison with those with low NK cell activity.

Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment

“…NK cell number and activity negatively correlate with the clinical stage of the disease, suggesting that multiple myeloma growth interferes with the NK cell ability to counteract tumor expansion (20)(21)(22).…”

“…The exclusion from bone marrow of NK cells endowed with the higher effector capacity represents a novel mechanism of immune evasion applied by multiple myeloma cells and may be one of the underlying causes of several NK cell functional abnormalities observed in multiple myeloma patients during disease progression (20,22,48). The data presented herein bring to the fore the unique properties of bone marrow microenviroment, and first highlight the importance of the altered trafficking of selected bone marrow NK cell effector populations mediated by multiple myeloma-driven dysregulation of bone marrow chemokine/chemokine receptor axes.…”

Variable Natural Killer Cell Activity in Hematological Malignancies at Diagnosis

“…AML patients with defective NK cells had a signi cantly higher risk of relapse [25]. MM patients showed a decreased NKA with advanced clinical stage, and patients with a high NKA after chemotherapy showed better survival than patients with a low NKA [26]. Interestingly, lenalidomide and pomalidomide for MM treatment stimulate NK cells [27].…”

Natural killer cell recognition of in vivo drug-induced senescent multiple myeloma cells

“…Previous studies have disclosed a pivotal role for NK cells in the immune response against MM. [32][33][34][35][36][37] To this regard, our group has demonstrated that a number of therapeutic drugs, including genotoxic agents, can boost the expression of NKG2D and DNAM-1 ligands on MM cells in vitro and ex vivo, and can enhance NK cell antitumor activity. 25,28,[38][39][40][41] Moreover, our findings also show that the enhanced expression of activating ligands on MM cells after the administration of genotoxic drugs such as doxorubicin and melphalan at doses that fail to induce apoptosis, is mediated by the DDR activation via ATM/ATR, and is associated with a drug-induced tumor cell senescent phenotype.…”