UC Irvine

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of innate immunecells that have the capacity to suppress adaptive immune responses. In cancer patients, increased numbers of MDSCs in circulation correlate with advanced clinical stages, increased metastatic progression and immune suppression. MDSCs can be further classified into granulocytic MDSCs (G-MDSCs) and monocytic MDSC (M-MDSCs). However, since MDSCs, normal neutrophil granulocytes, and monocytes are defined by the same flow cytometry markers (CD11b+Gr1+), finding MDSC-specific markers is essential. We use a breast cancer mouse model (MMTV-PyMT) to define the cellular and molecular properties of MDSCs in single cell resolution. To test the capacity of CD11b+Gr1+ cells to inhibit immune responses, CD11b+Gr1+ cells from PyMT and wild type (WT) mice were sorted by fluorescence-activated cell sorting (FACS) from bone marrow, lung, and spleen, and subjected to a T cell activation assay in co-culture with T cells. We found that spleen-derived CD11b+Gr1+ cells from PyMT significantly suppressed CD4 and CD8 T cell proliferation, while CD11b+Gr1+ cells from bone marrow and lung showed no effect on T cell proliferation. Therefore single-cell RNA sequencing (scRNAseq) was used to compare MDSC-containing splenic myeloid cells from breast tumor bearing mice to wildtype controls. Our computational analysis of 14,646 single cell transcriptomes revealed a MDSCs gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers model and human. Additionally, our data provides a MDSC-specific gene signature and identified specific surface markers for MDSCs detection and enrichment in this breast cancer model and human. Our studies provide crucial insight into the biology of MDSCs, which may ultimately reveal novel markers and therapeutic avenues to improve cancer immunotherapy.