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Comprehensive characterization of the multiple myeloma immune microenvironment using integrated scRNA-seq, CyTOF, and CITE-seq analysis


 As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of Multiple Myeloma (MM) bone marrow samples from 18 patients assessed by single-cell RNA-seq (scRNA-seq), mass cytometry (CyTOF), and Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) to understand the concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while variations are observed in T cells, macrophages, and monocytes. Concordance and correlation analysis of cell type marker gene expression across different modalities highlighted the importance of choosing cell type marker genes best suited to particular modalities. By integrating data from these three assays, we found International Staging System (ISS) stage 3 patients exhibited decreased CD4+ T/ CD8+ T cells ratio. Moreover, we observed upregulation of RAC2 and PSMB9, in NK cells of fast progressors (FP) compared to those of non-progressors (NP), as revealed by both scRNA-seq and CITE-seq RNA measurement. This detailed examination of the immune microenvironment in MM using multiple single cell technologies revealed markers associated with MM rapid progression which will be further characterized by the full-scale immune atlas project.