RT Journal Article
SR Electronic
T1 Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics
JF Science Immunology
JO Sci. Immunol.
FD American Association for the Advancement of Science
SP eaay6017
DO 10.1126/sciimmunol.aay6017
VO 5
IS 44
A1 Alshetaiwi, Hamad
A1 Pervolarakis, Nicholas
A1 McIntyre, Laura Lynn
A1 Ma, Dennis
A1 Nguyen, Quy
A1 Rath, Jan Akara
A1 Nee, Kevin
A1 Hernandez, Grace
A1 Evans, Katrina
A1 Torosian, Leona
A1 Silva, Anushka
A1 Walsh, Craig
A1 Kessenbrock, Kai
YR 2020
UL http://immunology.sciencemag.org/content/5/44/eaay6017.abstract
AB 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.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.