Research ResourcesTUMOR IMMUNOLOGY

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

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Science Immunology  21 Feb 2020:
Vol. 5, Issue 44, eaay6017
DOI: 10.1126/sciimmunol.aay6017

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Getting a hold on MDSCs

How myeloid-derived suppressor cells (MDSCs) arise and whether they can be therapeutically targeted akin to exhausted T cells are both areas of active investigation. A persistent challenge in studying MDSCs has been the identification of MDSC-specific cell surface markers that can facilitate their isolation and characterization. Here, by carrying out scRNAseq in a mouse model of breast cancer, Alshetaiwi et al. have defined gene signatures that distinguish MDSCs from other myeloid and granulocytic cells. By mining these datasets, they have identified CD84 to be a robust cell surface marker for identification of MDSCs in both human and murine breast cancer. Whether their findings can be extended to MDSCs in other cancer settings remains to be seen.

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.

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