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Pazina T , MacFarlane AW , Bernabei L , Dulaimi E , Kotcher R , Yam C , Bezman NA , Robbins MD , Ross EA , Campbell KS , Cohen AD
Alterations of NK Cell Phenotype in the Disease Course of Multiple Myeloma
Cancers (Basel). 2021 Jan 10;13(2)
PMID: 33435153    PMCID: PMC7827733    URL: https://www.ncbi.nlm.nih.gov/pubmed/33435153
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Abstract
Accumulating evidence demonstrates important roles for natural killer (NK) cells in controlling multiple myeloma (MM). A prospective flow cytometry-based analysis of NK cells in the blood and bone marrow (BM) of MM patient subgroups was performed (smoldering (SMM), newly diagnosed (ND), relapsed/refractory, (RR) and post-stem cell transplantation (pSCT)). Assessments included the biomarker expression and function of NK cells, correlations between the expression of receptors on NK cells with their ligands on myeloma cells, and comparisons between MM patient subgroups and healthy controls. The most striking differences from healthy controls were found in RR and pSCT patients, in which NK cells were less mature and expressed reduced levels of the activating receptors DNAM-1, NKG2D, and CD16. These differences were more pronounced in the BM than in blood, including upregulation of the therapeutic targets TIM3, TIGIT, ICOS, and GITR. Their expression suggests NK cells became exhausted upon chronic encounters with the tumor. A high expression of SLAMF7 on blood NK cells correlated with shorter progression-free survival. This correlation was particularly evident in ND patients, including on mature CD56(dim) NK cells in the BM. Thus, our NK cell analysis identified possible therapeutic targets in MM and a biomarker with prognostic potential for disease progression.
Notes
2072-6694 Pazina, Tatiana MacFarlane, Alexander W 4th Bernabei, Luca Orcid: 0000-0002-0213-8914 Dulaimi, Essel Kotcher, Rebecca Yam, Clinton Bezman, Natalie A Robbins, Michael D Ross, Eric A Campbell, Kerry S Orcid: 0000-0003-4665-7326 Cohen, Adam D P30 CA006927/CA/NCI NIH HHS/United States CA06927/NH/NIH HHS/United States CA204-016, CA204-157/Bristol-Myers Squibb/ Journal Article Cancers (Basel). 2021 Jan 10;13(2):226. doi: 10.3390/cancers13020226.