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Cross center single-cell RNA sequencing study of the immune microenvironment in rapid progressing multiple myeloma.

作者信息

Pilcher William, Thomas Beena E, Bhasin Swati S, Jayasinghe Reyka G, Yao Lijun, Gonzalez-Kozlova Edgar, Dasari Surendra, Kim-Schulze Seunghee, Rahman Adeeb, Patton Jonathan, Fiala Mark, Cheloni Giulia, Kourelis Taxiarchis, Dhodapkar Madhav V, Vij Ravi, Mehr Shaadi, Hamilton Mark, Cho Hearn Jay, Auclair Daniel, Avigan David E, Kumar Shaji K, Gnjatic Sacha, Ding Li, Bhasin Manoj

机构信息

Aflac Cancer and Blood Disorders Center, Atlanta, GA, USA.

Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA, USA.

出版信息

NPJ Genom Med. 2023 Jan 26;8(1):3. doi: 10.1038/s41525-022-00340-x.


DOI:10.1038/s41525-022-00340-x
PMID:36702834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9879959/
Abstract

Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM's progression is facilitated by complex interactions with the surrounding bone marrow (BM) cells, forming a microenvironment that supports tumor growth and drug resistance. Understanding the immune microenvironment is key to identifying factors that promote rapid progression of MM. To accomplish this, we performed a multi-center single-cell RNA sequencing (scRNA-seq) study on 102,207 cells from 48 CD138 BM samples collected at the time of disease diagnosis from 18 patients with either rapid progressing (progression-free survival (PFS) < 18 months) or non-progressing (PFS > 4 years) disease. Comparative analysis of data from three centers demonstrated similar transcriptome profiles and cell type distributions, indicating subtle technical variation in scRNA-seq, opening avenues for an expanded multicenter trial. Rapid progressors depicted significantly higher enrichment of GZMK and TIGIT exhausted CD8 T-cells (P = 0.022) along with decreased expression of cytolytic markers (PRF1, GZMB, GNLY). We also observed a significantly higher enrichment of M2 tolerogenic macrophages in rapid progressors and activation of pro-proliferative signaling pathways, such as BAFF, CCL, and IL16. On the other hand, non-progressive patients depicted higher enrichment for immature B Cells (i.e., Pre/Pro B cells), with elevated expression for markers of B cell development (IGLL1, SOX4, DNTT). This multi-center study identifies the enrichment of various pro-tumorigenic cell populations and pathways in those with rapid progressing disease and further validates the robustness of scRNA-seq data generated at different study centers.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/498d6a2b5e46/41525_2022_340_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/3a66edea2081/41525_2022_340_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/92e54e865b2b/41525_2022_340_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/4e54612839d7/41525_2022_340_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/e1f5804d7376/41525_2022_340_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/00d4aa697229/41525_2022_340_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/498d6a2b5e46/41525_2022_340_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/3a66edea2081/41525_2022_340_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/92e54e865b2b/41525_2022_340_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/4e54612839d7/41525_2022_340_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/e1f5804d7376/41525_2022_340_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/00d4aa697229/41525_2022_340_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cf/9879959/498d6a2b5e46/41525_2022_340_Fig6_HTML.jpg

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Cross center single-cell RNA sequencing study of the immune microenvironment in rapid progressing multiple myeloma.

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引用本文的文献

[1]
Identification of malignant cells in single-cell transcriptomics data.

Commun Biol. 2025-8-22

[2]
Identification of the Distinct Immune Microenvironment Features Associated with Progression Following High-Dose Melphalan and Autologous Stem Cell Transplant in Multiple Myeloma.

Cancer Immunol Res. 2025-7-2

[3]
T cell phenotype and clonality changes in myeloma patients with short overall survival.

JCI Insight. 2025-4-22

[4]
Integrative single-cell and spatial transcriptome analysis reveals heterogeneity of human liver progenitor cells.

Hepatol Commun. 2025-2-26

[5]
Multiple Myeloma Insights from Single-Cell Analysis: Clonal Evolution, the Microenvironment, Therapy Evasion, and Clinical Implications.

Cancers (Basel). 2025-2-14

[6]
Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?

Ann Hematol. 2025-2

[7]
Polyfunctional CD8CD226RUNX2 effector T cells are diminished in advanced stages of chronic lymphocytic leukemia.

Mol Oncol. 2025-5

[8]
A single-cell transcriptomic map of the murine and human multiple myeloma immune microenvironment across disease stages.

J Hematol Oncol. 2024-11-7

[9]
Single-cell sequencing analysis of multiple myeloma heterogeneity and identification of new theranostic targets.

Cell Death Dis. 2024-9-14

[10]
Granzyme K drives a newly-intentified pathway of complement activation.

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本文引用的文献

[1]
Human M1 macrophages express unique innate immune response genes after mycobacterial infection to defend against tuberculosis.

Commun Biol. 2022-5-19

[2]
Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases.

Front Immunol. 2022

[3]
Survival Genie, a web platform for survival analysis across pediatric and adult cancers.

Sci Rep. 2022-2-23

[4]
Stepwise immune alterations in multiple myeloma progression.

Nat Cancer. 2020-5

[5]
Reinvestigation of Classic T Cell Subsets and Identification of Novel Cell Subpopulations by Single-Cell RNA Sequencing.

J Immunol. 2022-1-15

[6]
IRF4 Has a Unique Role in Early B Cell Development and Acts Prior to CD21 Expression to Control Marginal Zone B Cell Numbers.

Front Immunol. 2021

[7]
Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation.

Nat Commun. 2021-11-25

[8]
Cancer-associated fibroblasts induce monocytic myeloid-derived suppressor cell generation via IL-6/exosomal miR-21-activated STAT3 signaling to promote cisplatin resistance in esophageal squamous cell carcinoma.

Cancer Lett. 2021-10-10

[9]
Integrated analysis of multimodal single-cell data.

Cell. 2021-6-24

[10]
Cryopreservation Preserves Cell-Type Composition and Gene Expression Profiles in Bone Marrow Aspirates From Multiple Myeloma Patients.

Front Genet. 2021-4-21

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