Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/s41590-021-00931-3

Type

Journal article

Journal

Nat Immunol

Publication Date

06/2021

Volume

22

Pages

769 - 780

Keywords

Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow, Cell Line, Tumor, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Mesenchymal Stem Cells, Middle Aged, Multiple Myeloma, Neoplasm Recurrence, Local, Primary Cell Culture, Prospective Studies, RNA-Seq, Single-Cell Analysis, Tumor Microenvironment