Comprehensive Characterization of the Multiple Myeloma Immune Microenvironment Using Integrated scRNA-seq, CyTOF, and CITE-seq Analysis.

Autor:	Yao L; Washington University School of Medicine, Saint Louis, Missouri., Jayasinghe RG; Washington University School of Medicine, Saint Louis, Missouri., Lee BH; Icahn School of Medicine at Mt. Sinai, New York, New York., Bhasin SS; Emory University, Atlanta, Georgia., Pilcher W; Emory University, Atlanta, Georgia., Doxie DB; Emory University, Atlanta, Georgia., Gonzalez-Kozlova E; Icahn School of Medicine at Mt. Sinai, New York, New York., Dasari S; Mayo Clinic, Rochester, Minnesota., Fiala MA; Washington University School of Medicine, Saint Louis, Missouri., Pita-Juarez Y; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts., Strausbauch M; Mayo Clinic, Rochester, Minnesota., Kelly G; Icahn School of Medicine at Mt. Sinai, New York, New York., Thomas BE; Emory University, Atlanta, Georgia., Kumar SK; Mayo Clinic, Rochester, Minnesota., Cho HJ; Icahn School of Medicine at Mt. Sinai, New York, New York.; Multiple Myeloma Research Foundation, Norwalk, Connecticut., Anderson E; Mayo Clinic, Rochester, Minnesota., Wendl MC; Washington University School of Medicine, Saint Louis, Missouri., Dawson T; Icahn School of Medicine at Mt. Sinai, New York, New York., D'souza D; Icahn School of Medicine at Mt. Sinai, New York, New York., Oh ST; Washington University School of Medicine, Saint Louis, Missouri., Cheloni G; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts., Li Y; Mayo Clinic, Rochester, Minnesota., DiPersio JF; Washington University School of Medicine, Saint Louis, Missouri., Rahman AH; Icahn School of Medicine at Mt. Sinai, New York, New York., Dhodapkar KM; Emory University, Atlanta, Georgia., Kim-Schulze S; Icahn School of Medicine at Mt. Sinai, New York, New York., Vij R; Washington University School of Medicine, Saint Louis, Missouri., Vlachos IS; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts., Mehr S; Multiple Myeloma Research Foundation, Norwalk, Connecticut., Hamilton M; Multiple Myeloma Research Foundation, Norwalk, Connecticut., Auclair D; Multiple Myeloma Research Foundation, Norwalk, Connecticut., Kourelis T; Mayo Clinic, Rochester, Minnesota., Avigan D; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts., Dhodapkar MV; Emory University, Atlanta, Georgia., Gnjatic S; Icahn School of Medicine at Mt. Sinai, New York, New York., Bhasin MK; Emory University, Atlanta, Georgia., Ding L; Washington University School of Medicine, Saint Louis, Missouri.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2022 Oct 25; Vol. 2 (10), pp. 1255-1265. Date of Electronic Publication: 2022 Oct 25 (Print Publication: 2022).
DOI:	10.1158/2767-9764.CRC-22-0022
Abstrakt:	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. Competing Interests: S.K. Kumar reports other from Abbvie, Amgen, BMS, Janssen, Roche-Genentech, Takeda, AstraZeneca, Bluebird Bio, Epizyme, Secura Biotherapeutics, Monterosa therapeutics, Trillium, Loxo Oncology, K36, Sanofi, ArcellX; personal fees from ncopeptides, Beigene, Antengene, GLH Pharma; and grants from Abbvie, Amgen, Allogene, AstraZeneca, BMS, Carsgen, GSK, Janssen, Novartis, Roche-Genentech, Takeda, Regeneron, Molecular Templates outside the submitted work. H.J. Cho reports other from The Multiple Myeloma Research Foundation during the conduct of the study; grants from BMS and Takeda outside the submitted work. A.H. Rahman reports grants from Multiple Myeloma Research Foundation during the conduct of the study; grants from Celgene/BMS and personal fees from Fluidigm outside the submitted work. D. Avigan reports other from BMS, Chugai, Sanofi, Merk, and Paraexel; and grants from MMRF outside the submitted work. S. Gnjatic reports grants from Multiple Myeloma Research Foundation during the conduct of the study; grants from Regeneron, Boehringer Ingelheim, BMS, Genentech, Jannsen R&D, Takeda, and EMD Serono outside the submitted work. No disclosures were reported by the other authors. (© 2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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