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Cited by 374Multiple Myeloma Research and TreatmentsLymphoma Diagnosis and TreatmentCancer Immunotherapy and Biomarkers

Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma

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Zavidij, Oksana, Haradhvala, Nicholas J., Mouhieddine, Tarek H., Sklavenitis-Pistofidis, Romanos, Cai, Songjie, Reidy, Mairead, Rahmat, Mahshid, Flaifel, Abdallah +21 more·2020·Nature Cancer
DOI 10.1038/s43018-020-0053-3PMC PMC7785110
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Abstract

Precursor states of Multiple Myeloma (MM) and its native tumor microenvironment need in-depth molecular characterization to better stratify and treat patients at risk. Using single-cell RNA sequencing of bone marrow cells from precursor stages, MGUS and smoldering myeloma (SMM), to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient progression. We find NK cell abundance is frequently increased in early stages, and associated with altered chemokine receptor expression. As early as SMM, we show loss of GrK+ memory cytotoxic T-cells, and show their critical role in MM immunosurveillance in mouse models. Finally, we report MHC class II dysregulation in CD14+ monocytes, which results in T cell suppression in vitro. These results provide a comprehensive map of immune changes at play over the evolution of pre-malignant MM, which will help develop strategies for immune-based patient stratification.

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  • Several patterns of immune dysregulation have been reported in MGUS and SMM using single cell RNA sequencing.

    “Several patterns of dysregulation have been reported using single cell RNA sequencing.82,83,91-93”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [83]

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References 65 · Cited by 374

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Authors
Zavidij, O., Haradhvala, N. J., Mouhieddine, T. H., Sklavenitis-Pistofidis, R., Cai, S., Reidy, M., Rahmat, M., Flaifel, A., Ferland, B., Su, N. K., Agius, M. P., Park, J., Manier, S., Bustoros, M., Huynh, D., Capelletti, M., Berrios, B., Liu, C.-J., He, M. X., Braggio, E., Fonseca, R., Maruvka, Y. E., Guerriero, J. L., Goldman, M., Van Allen, E. M., McCarroll, S. A., Azzi, J., Getz, G., & Ghobrial, I. M.
Affiliations
  • Broad Institute (US)
  • Brigham and Women's Hospital (US)
  • Dana-Farber Cancer Institute (US)
  • Harvard University (US)
  • Mayo Clinic in Arizona (US)
Corresponding author
  • Getz, Gad
  • Ghobrial, Irene M.
ORCID
Venue
Nature Cancer
Publisher
Springer Science and Business Media LLC
Published
2020-04-27
Volume
1
Issue
5
Pages
493-506
ISSN
2662-1347 (ISSN-L)
DOI
10.1038/s43018-020-0053-3
PMC
PMC7785110
OpenAlex
W3018331841
Cited by
374
References
65
Citations by year
2026: 53 · 2025: 65 · 2024: 62 · 2023: 66 · 2022: 60 · 2021: 45 · 2020: 21 · 2019: 2
FWCI
30.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • European Hematology Association (TRTH177)
  • National Cancer Institute (R01CA181683, R01CA205954, P30CA006516)
  • National Institute of General Medical Sciences (T32GM008313)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
multiple myeloma, tumor immune microenvironment, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, natural killer cells, chemokine receptors, immune surveillance, CD14+ monocytes, T cell suppression, bone marrow, disease progression, patient stratification
MeSH terms
Smoldering Multiple Myeloma, Animals, Humans, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Sequence Analysis, RNA, Mice, Tumor Microenvironment

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