The multiple myeloma microenvironment is defined by an inflammatory stromal cell landscape

Single-cell RNA sequencing datasets of the immune and non-hematopoietic bone marrow microenvironment and plasma cells of newly diagnosed individuals with multiple myeloma and non-cancer control patients as published by De Jong et al., Nat Immunol. 2021 Jun;22(6):769-780 doi: 10.1038/s41590-021-00931-3 Abstract: Progression and persistence of malignancies are influenced by the local tumor microenvironment, and future eradication of currently incurable tumors will, in part, hinge on our understanding of malignant cell biology in the context of their nourishing surroundings. Here, we generated paired single-cell transcriptomic datasets of tumor cells and the bone marrow immune and stromal microenvironment in multiple myeloma. These analyses identified myeloma-specific inflammatory mesenchymal stromal cells, which spatially colocalized with tumor cells and immune cells and transcribed genes involved in tumor survival and immune modulation. Inflammatory stromal cell signatures were driven by stimulation with proinflammatory cytokines, and analyses of immune cell subsets suggested interferon-responsive effector T cell and CD8+ stem cell memory T cell populations as potential sources of stromal cell-activating cytokines. Tracking stromal inflammation in individuals over time revealed that successful antitumor induction therapy is unable to revert bone marrow inflammation, predicting a role for mesenchymal stromal cells in disease persistence.