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

摘要

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptiveimmune 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 todetermine the molecular features of breast cancer–associated MDSCs using the widely studied mouse model basedon 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 MDSCcontainingsplenic myeloid cells from breast tumor–bearing mice with wild-type controls. Our computationalanalysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturationtrajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific genesignature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.