학술논문
The multiple myeloma microenvironment is defined by an inflammatory stromal cell landscape
Document Type
Report
Author
de Jong, Madelon M. E.; Kellermayer, Zoltán; Papazian, Natalie; Tahri, Sabrin; Hofste op Bruinink, Davine; Hoogenboezem, Remco; Sanders, Mathijs A.; van de Woestijne, Pieter; Bos, P. Koen; Khandanpour, Cyrus; Vermeulen, Jessica; Moreau, Phlippe; van Duin, Mark; Broijl, Annemiek; Sonneveld, Pieter; Cupedo, Tom
Source
Nature Immunology. June 2021, Vol. 22 Issue 6, p769, 12 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Madelon M. E. de Jong [sup.1] , Zoltán Kellermayer [sup.1] , Natalie Papazian [sup.1] , Sabrin Tahri [sup.1] , Davine Hofste op Bruinink [sup.1] , Remco Hoogenboezem [sup.1] , [...]
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.sup.+ 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. Multiple myeloma disease progression and therapy response are influenced by the bone marrow niche in which the tumor cells reside. To characterize this supportive niche, Cupedo and colleagues use single-cell transcriptomic analysis of bone marrow stromal cell populations from individuals with multiple myeloma. They identify a myeloma-specific inflammatory mesenchymal stromal cell (iMSC) population that spatially colocalizes with tumor cells. Anti-myeloma induction therapy does not influence iMSC presence, suggesting a role for bone marrow inflammation in myeloma persistence or relapse.
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.sup.+ 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. Multiple myeloma disease progression and therapy response are influenced by the bone marrow niche in which the tumor cells reside. To characterize this supportive niche, Cupedo and colleagues use single-cell transcriptomic analysis of bone marrow stromal cell populations from individuals with multiple myeloma. They identify a myeloma-specific inflammatory mesenchymal stromal cell (iMSC) population that spatially colocalizes with tumor cells. Anti-myeloma induction therapy does not influence iMSC presence, suggesting a role for bone marrow inflammation in myeloma persistence or relapse.