NK cell dysregulation in the multiple myeloma: insights from multi-modal profiling of the bone marrow microenvironment 2812

Description Innate immune cells (NK & NK-T-like cells) are important effector cells for anti-tumor responses in multiple myeloma (MM), a hematological malignancy where clonal plasma cells expand in the bone marrow (BM). There is a disjointed picture of the NK cell phenotype in the MM tumor microenvironment (TME). Using a combination of traditional flow cytometry, spectral flow cytometry, & single-cell RNA sequencing with the addition of CITE-seq, we sought to gain a greater understanding of NK cells in the TME of MM patients by sampling BM from healthy and newly diagnosed cohorts. We observed an increase in total NK cells, but a decrease in the CD56DimCD16+ NK cell subset. CD56DimCD16+ NK cells displayed a more mature, terminally differentiated phenotype in MM compared to controls. Further, we report that CD158a & CD158f were altered within this subset. Additional characterization of CD57+ NK cells, increased in MM, found that this subset was enriched in high frequencies of KIR-expressing cells & granzyme transcripts. This study illustrated the profiles of NK cells in the BM immune cell microenvironment using flow cytometry and CITE-seq. This methodology facilitated the integration of surface marker expression with corresponding gene expression patterns, providing a robust framework for analyzing the TME. For Research-Use Only. Not for use in diagnostic or therapeutic procedures. BD and the BD Logo are trademarks of Becton, Dickinson and Company.