Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics.

Details

Serval ID
serval:BIB_95EE1B275C25
Type
Article: article from journal or magazin.
Collection
Publications
Title
Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics.
Journal
Science immunology
Author(s)
Alshetaiwi H., Pervolarakis N., McIntyre L.L., Ma D., Nguyen Q., Rath J.A., Nee K., Hernandez G., Evans K., Torosian L., Silva A., Walsh C., Kessenbrock K.
ISSN
2470-9468 (Electronic)
ISSN-L
2470-9468
Publication state
Published
Issued date
21/02/2020
Peer-reviewed
Oui
Volume
5
Number
44
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.
Pubmed
Create date
27/02/2020 15:39
Last modification date
28/10/2020 13:52
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