Myeloid-Derived Suppressor Cells – Using Flow Cytometry to Understand these Immune Suppressive Heavyweights in Cancer

MDSCs

Myeloid-derived Suppressor Cells (MDSCs) have come to be known as key regulators of the immune system, particularly with their role in promoting tumor progression. At least two major subsets of MDSCs have been defined in mouse models based on phenotypic features - monocytic-MDSCS (M-MDSCs) and polymorphonuclear-MDSCs (PMN-MDSC). Characterization of human MDSCs in cancer patients has revealed a more complicated picture of MDSC subsets. Flow cytometry has been essential characterizing MDSCs and understanding their role in different cancers. Here are three ways flow cytometry has been invaluable to understanding MDSCs.

Basic Phenotyping: Advances in flow cytometry have been critical to defining the key phenotypic markers of MDSC subsets. In mice, M-MDSCs are defined as CD11b⁺Ly6C^hiLy6G^-, and PMN-MDSCs are CD11b⁺Ly6C^loLy6G⁺. Human MDSC subsets have been shown to be more variable, especially in cancer and under inflammatory conditions, but M-MDSCs are typically defined as HLADR^-CD11b⁺CD14⁺CD15^-CD33^hi, whereas PMN-MDSC are HLADR^-CD11b⁺CD14^-CD15⁺CD33^mid.
MDSCs versus similar cell types: On of the defining features of MDSCs is their high degree of plasticity. Although MDSCs are consider a unique cell type, they share features with monocytes and neutrophils, and flow cytometry coupled with gene expression profiling and mass cytometry have defined gene signatures and metabolic features unique to MDSCs.
MDSCs in tumors: MDSCs are well known for their ability to migrate into tumors, typically through sensing of different cytokines and chemokines. Within tumors, MDSCs show great plasticity, and M-MDSCs can differentiated into tumor associated macrophages. PMN-MDSCs are a shorter-lived subset with many features shared with neutrophils, and as such their plasticity is less well understood. Flow cytometry is critical to tracking MDSCs as they migrate and change in tumors.

MDSCs provide critical insights into clinical outcomes for cancer patients. Consider working with a flow cytometry expert if you plan to study and track MDSC subsets in preclinical or clinical immuno-oncology research.