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Single-cell RNA-Seq of follicular lymphoma reveals malignant B-cell types and coexpression of T-cell immune checkpoints.
- Source :
-
Blood [Blood] 2019 Mar 07; Vol. 133 (10), pp. 1119-1129. Date of Electronic Publication: 2018 Dec 27. - Publication Year :
- 2019
-
Abstract
- Follicular lymphoma (FL) is a low-grade B-cell malignancy that transforms into a highly aggressive and lethal disease at a rate of 2% per year. Perfect isolation of the malignant B-cell population from a surgical biopsy is a significant challenge, masking important FL biology, such as immune checkpoint coexpression patterns. To resolve the underlying transcriptional networks of follicular B-cell lymphomas, we analyzed the transcriptomes of 34 188 cells derived from 6 primary FL tumors. For each tumor, we identified normal immune subpopulations and malignant B cells, based on gene expression. We used multicolor flow cytometry analysis of the same tumors to confirm our assignments of cellular lineages and validate our predictions of expressed proteins. Comparison of gene expression between matched malignant and normal B cells from the same patient revealed tumor-specific features. Malignant B cells exhibited restricted immunoglobulin (Ig) light chain expression (either Igκ or Igλ), as well the expected upregulation of the BCL2 gene, but also downregulation of the FCER2 , CD52 , and major histocompatibility complex class II genes. By analyzing thousands of individual cells per patient tumor, we identified the mosaic of malignant B-cell subclones that coexist within a FL and examined the characteristics of tumor-infiltrating T cells. We identified genes coexpressed with immune checkpoint molecules, such as CEBPA and B2M in regulatory T (Treg) cells, providing a better understanding of the gene networks involved in immune regulation. In summary, parallel measurement of single-cell expression in thousands of tumor cells and tumor-infiltrating lymphocytes can be used to obtain a systems-level view of the tumor microenvironment and identify new avenues for therapeutic development.<br /> (© 2019 by The American Society of Hematology.)
- Subjects :
- Biopsy
CCAAT-Enhancer-Binding Proteins genetics
CD4-Positive T-Lymphocytes cytology
CD52 Antigen genetics
Cell Lineage
Flow Cytometry
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Hematopoietic Stem Cells cytology
Histocompatibility Antigens Class II metabolism
Humans
Immune System
Immunoglobulin G
Lectins, C-Type genetics
Leukocytes, Mononuclear cytology
Lymphoma, B-Cell blood
Lymphoma, Follicular blood
Palatine Tonsil metabolism
Receptors, IgE genetics
Sequence Analysis, RNA
Transcriptome
Tumor Microenvironment
beta 2-Microglobulin genetics
Lymphoma, B-Cell genetics
Lymphoma, Follicular genetics
T-Lymphocytes, Regulatory cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 133
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 30591526
- Full Text :
- https://doi.org/10.1182/blood-2018-08-862292