Mapping the cytotoxic landscape: an integrated analysis of T cell heterogeneity in the bone marrow microenvironment of multiple myeloma 2810

Description Multiple Myeloma (MM) is characterized by the clonal proliferation of plasma cells in the bone marrow (BM), which serves as the tumor microenvironment (TME). Despite treatment advances, MM remains incurable. Therefore, understanding the cytotoxic T-cell component of the TME may enable the development of better-targeted therapies. We characterized the cytotoxic T cells from the BM of MM & healthy cohorts using flow cytometry & single-cell RNA sequencing (scRNA-seq) with CITE-seq, enabling the high-resolution analysis of surface protein & transcriptomic changes within individual cells. We identified an expanded population of CD57+ cytotoxic T cells. This CD57+ subset had reduced expression of CD28 & did not express common exhaustion markers. These cells exhibited a bias towards polyfunctionality, however, both transcript & protein were expressed at lower levels than controls. Furthermore, scRNA-seq revealed enrichment of perforin & granzyme transcripts, further supporting the finding of a senescent cell with high cytotoxic potential. By combining flow cytometry with scRNA-seq & CITE-seq, this study mapped the changes in the BM TME. This approach allowed us to link surface marker expression with gene expression profiles, enabling a comprehensive analysis of the CD8+ T cells in TME of MM patients. For Research-Use Only. Not for use in diagnostic or therapeutic procedures. BD and the BD Logo are trademarks of Becton, Dickinson and Company.