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Comprehensive Characterization of the Multiple Myeloma Immune Microenvironment Using Integrated scRNA-seq, CyTOF, and CITE-seq Analysis
Open accessPublished version of a preprint
Abstract
As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of multiple myeloma bone marrow samples from 18 patients assessed by single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to understand the concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while variations are observed in T cells, macrophages, and monocytes. Concordance and correlation analysis of cell type marker gene expression across different modalities highlighted the importance of choosing cell type marker genes best suited to particular modalities. By integrating data from these three assays, we found International Staging System stage 3 patients exhibited decreased CD4+ T/CD8+ T cells ratio. Moreover, we observed upregulation of RAC2 and PSMB9, in natural killer cells of fast progressors compared with those of nonprogressors, as revealed by both scRNA-seq and CITE-seq RNA measurement. This detailed examination of the immune microenvironment in multiple myeloma using multiple single-cell technologies revealed markers associated with multiple myeloma rapid progression which will be further characterized by the full-scale immune atlas project. Significance: scRNA-seq, CyTOF, and CITE-seq are increasingly used for evaluating cellular heterogeneity. Understanding their concordances is of great interest. To date, this study is the most comprehensive examination of the measurement of the immune microenvironment in multiple myeloma using the three techniques. Moreover, we identified markers predicted to be significantly associated with multiple myeloma rapid progression.
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Cites
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“In contrast, we observed drastic differences of some marker genes between RNA and ADT expression in CITE-seq, probably due to the RNA dropout (21) and shorter half-lives of mRNAs versus proteins (15).”
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Metadata
- Authors
- Yao, L., Jayasinghe, R. G., Lee, B. H., Bhasin, S. S., Pilcher, W., Doxie, D. B., Gonzalez-Kozlova, E., Dasari, S., Fiala, M. A., Pita-Juarez, Y., Strausbauch, M., Kelly, G., Thomas, B. E., Kumar, S. K., Cho, H. J., Anderson, E., Wendl, M. C., Dawson, T., D'souza, D., Oh, S. T., Cheloni, G., Li, Y., DiPersio, J. F., Rahman, A. H., Dhodapkar, K. M., Kim-Schulze, S., Vij, R., Vlachos, I. S., Mehr, S., Hamilton, M., Auclair, D., Kourelis, T., Avigan, D., Dhodapkar, M. V., Gnjatic, S., Bhasin, M. K., & Ding, L.
- Affiliations
- Washington University in St. Louis (US)
- Icahn School of Medicine at Mount Sinai (US)
- Emory University (US)
- 2Icahn School of Medicine at Mt. Sinai, New York, New York.
- Mayo Clinic (US)
- 5Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
- Multiple Myeloma Research Foundation (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Ding, Li
- ORCID
- Yao, Lijun
- Jayasinghe, Reyka G.
- Lee, Brian H.
- Bhasin, Swati S.
- Pilcher, William
- Doxie, Deon Bryant
- Dasari, Surendra
- Fiala, Mark A.
- Pita-Juarez, Yered
- Kelly, Geoffrey
- Kumar, Shaji K.
- Cho, Hearn Jay
- Wendl, Michael C.
- Dawson, Travis
- Oh, Stephen T.
- Cheloni, Giulia
- Li, Ying
- DiPersio, John F.
- Rahman, Adeeb H.
- Dhodapkar, Kavita M.
- Vij, Ravi
- Vlachos, Ioannis S.
- Mehr, Shaadi
- Hamilton, Mark
- Auclair, Daniel
- Kourelis, Taxiarchis
- Avigan, David
- Dhodapkar, Madhav V.
- Gnjatic, Sacha
- Bhasin, Manoj K.
- Ding, Li
- Venue
- Cancer Research Communications
- Published
- 2022-10-25
- Volume
- 2
- Issue
- 10
- Pages
- 1255-1265
- ISSN
- 2767-9764 (ISSN-L)
- PMC
- PMC10035369
- OpenAlex
- W4293757902
- Cited by
- 45
- References
- 5
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 5 · 2023: 11
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Research Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- Funders
- Multiple Myeloma Research Foundation
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- multiple myeloma, tumor immune microenvironment, bone marrow, single-cell RNA sequencing, mass cytometry, CITE-seq, multi-omics integration, assay concordance, cell type markers, CD4/CD8 ratio, natural killer cells, Rac2, PSMB9, disease progression, macrophages, monocytes
- MeSH terms
- Single-Cell Gene Expression Analysis, Humans, Multiple Myeloma, Pilot Projects, CD8-Positive T-Lymphocytes, Tumor Microenvironment, Transcriptome
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