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.

单细胞RNA测序数据集描述

摘要：恶性肿瘤的进展与持续存在受局部肿瘤微环境的影响，而未来对目前尚无治愈方法的肿瘤的根除，在一定程度上将取决于我们对恶性肿瘤细胞生物学在其滋养环境中的理解。在此，我们生成了多发性骨髓瘤中肿瘤细胞与骨髓免疫和基质微环境的配对单细胞转录组数据集。这些分析鉴定出与骨髓瘤特异性炎症间充质基质细胞，这些细胞在空间上与肿瘤细胞和免疫细胞共定位，并转录涉及肿瘤生存和免疫调节的基因。炎症基质细胞特征由促炎细胞因子的刺激驱动，而免疫细胞亚群的分析表明干扰素反应性效应T细胞和CD8+干细胞记忆T细胞群体可能是基质细胞激活细胞因子的潜在来源。对个体随时间追踪基质炎症发现，成功的抗肿瘤诱导治疗无法逆转骨髓炎症，预示间充质基质细胞在疾病持续过程中的作用。