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

Nat Immunol. 2021 Jun;22(6):769-780. doi: 10.1038/s41590-021-00931-3. Epub 2021 May 20.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow / drug effects
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Male
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / pathology
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control
  • Primary Cell Culture
  • Prospective Studies
  • RNA-Seq
  • Single-Cell Analysis
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*