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MULTIPLE MYELOMA

Inflammatory stromal cells in the myeloma microenvironment

Nature Immunology volume 22, pages 677–678 (2021)Cite this article

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Single-cell RNA sequencing identifies an inflammatory subpopulation of mesenchymal stromal cells in patients with multiple myeloma.

Multiple myeloma (MM) is a deadly plasma cell malignancy of the bone marrow that reoccurs after treatment1. Recent sequencing endeavors have unveiled many of the key genomic drivers acquired by MM, yet the majority of these also occur in patients at the asymptomatic precursor stages of the disease that may never progress to overt MM1. Mounting evidence, such as the consistent growth of these precursors following transplant in mice, suggests that tumor-extrinsic mechanisms are probably key regulators of disease formation2. Indeed, the immune microenvironment is significantly altered in MM, and immune dysregulation is established early at the monoclonal gammopathy of undetermined significance (MGUS) stage3. The nonimmune microenvironment (mesenchymal stromal cells, MSCs) has been shown to support MM growth and induce drug resistance and immunomodulation4. Despite great scientific interest in the role of MSCs in MM disease progression, investigation of their role has been hampered by the low frequency of these cells in bone marrow aspirate samples and by challenges related to their in vitro expansion, which is often required to obtain sufficient numbers for experimentation. In this issue of Nature Immunology, de Jong et al.5 present the first study using single-cell RNA sequencing to profile natural MSCs, as well as immune and tumor cells, from individuals with MM (n = 13) and healthy donors (n = 7) to comprehensively characterize the nonimmune microenvironment in MM and its interactions with immune and tumor cells.

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Fig. 1: Model of the interaction between iMSCs and tumor and immune cells.

References

  1. Dhodapkar, M. V. Blood 128, 2599–2606 (2016).

    Article  CAS  Google Scholar 

  2. Das, R. et al. Nat. Med. 22, 1351–1357 (2016).

    Article  CAS  Google Scholar 

  3. Zavidij, O. et al. Nat. Cancer 1, 493–506 (2020).

    Article  Google Scholar 

  4. Reagan, M. R. & Ghobrial, I. M. Clin. Cancer Res. 18, 342–349 (2011).

    Article  Google Scholar 

  5. de Jong, M. E. M. et al. Nat. Immunol. https://doi.org/10.1038/s41590-021-00931-3 (2021).

    Article  PubMed  Google Scholar 

  6. Baryawno, N. et al. Cell 177, 1915–1932.e16 (2019).

    Article  CAS  Google Scholar 

  7. Lemaitre, L. et al. Int. J. Mol. Sci. 21, 3854 (2020).

    Article  CAS  Google Scholar 

  8. Vande Broek, I. et al. Br. J. Cancer 88, 855–862 (2003).

    Article  CAS  Google Scholar 

  9. Qian, H., Le Blanc, K. & Sigvardsson, M. J. Biol. Chem. 287, 25795–25807 (2012).

    Article  CAS  Google Scholar 

  10. Munshi, N. C. et al. Blood Adv. 4, 5988–5999 (2020).

    Article  Google Scholar 

  11. Alameda, D. et al. Haematologica 105, e470–e473 (2020).

    Article  Google Scholar 

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Author notes

  1. These authors contributed equally: Romanos Sklavenitis-Pistofidis, Nicholas J. Haradhvala.

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Romanos Sklavenitis-Pistofidis & Irene M. Ghobrial

  2. Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA, USA

    Romanos Sklavenitis-Pistofidis & Irene M. Ghobrial

  3. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Romanos Sklavenitis-Pistofidis, Nicholas J. Haradhvala, Gad Getz & Irene M. Ghobrial

  4. Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA

    Nicholas J. Haradhvala

  5. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Gad Getz

Authors
  1. Romanos Sklavenitis-Pistofidis
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  2. Nicholas J. Haradhvala
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  3. Gad Getz
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  4. Irene M. Ghobrial
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Corresponding author

Correspondence to Irene M. Ghobrial.

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Competing interests

R.S.P. has no competing interests to disclose. N.J.H. is a consultant for Constellation Pharmaceuticals. I.M.G has a consulting and advisory role with Celgene, Takeda, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals and Amgen and has received research funding/honoraria from Celgene, Takeda, Bristol-Myers Squibb, Janssen Pharmaceuticals and Amgen. G.G. receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig, MSIdetect, POLYSOLVER and TensorQTL. G.G. is a founder, consultant and holds privately held equity in Scorpion Therapeutics.

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Sklavenitis-Pistofidis, R., Haradhvala, N.J., Getz, G. et al. Inflammatory stromal cells in the myeloma microenvironment. Nat Immunol 22, 677–678 (2021). https://doi.org/10.1038/s41590-021-00947-9

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