Integrated scRNA-seq, CyTOF, and CITE-seq analysis of myeloma immune microenvironment

As part of the MMRF immune atlas pilot project, we compared immune cells of Multiple Myeloma (MM) bone marrow samples from 18 patients assessed by scRNA-seq, CyTOF, and CITE-seq to understand the concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while discrepancies are observed in T cells, macrophages, and monocytes. Concordance analysis of cell type marker gene expression across different modalities highlighted the importance of choosing marker genes best suited to particular modalities. By integrating data from these three assays, we found ISS stage 3 patients exhibited decreased CD4+ T/ CD8+ T cells ratio, and decreased expression of CD45RA relative to stage 2 patients. Moreover, we observed upregulation of ARPC5, XAF1, 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. In summary, our detailed examination of the immune microenvironment in MM using multiple single cell technologies revealed a set of consensus markers associated with disease progression which will be further characterized by the full-scale immune atlas project.