Abstract
Myeloid-derived suppressor cells (MDSCs) expand during pathological conditions in both humans and mice and their presence is linked to poor clinical outcomes for cancer patients. Studying MDSC immunosuppression is restricted by MDSCs’ rarity, short lifespan, heterogeneity, poor viability after freezing and the lack of MDSC-specific markers. In this review, we will compare identification and isolation strategies for human and murine MDSCs. We will also assess what direct and indirect immunosuppressive mechanisms have been attributed to MDSCs. While some immunosuppressive mechanisms are well-documented in mice, e.g., generation of ROS, direct evidence is still lacking in humans. In future, bulk or single-cell genomics could elucidate which phenotypic and functional phenotypes MDSCs adopt in particular microenvironments and help to identify potential targets for therapy.
Highlights
Within the tumor microenvironment (TME), myeloid-derived suppressor cells (MDSCs) are a rare group of myeloid cells with immunosuppressive capacities that accumulate in individuals with conditions that include cancer, and sepsis or chronic infection [2]
In humans, increased MDSC levels are correlated to poor prognoses for disease outcome, and ablating MDSCs in mice resulted in improved tumor control [9,10,11]
Condamine et al found that PMN-MDSCs overexpress lectin-type oxidized LDL receptor 1 (LOX-1) by comparing the transcriptomes of PMN-MDSCs and neutrophils from the blood of healthy donors, non-small cell lung carcinoma (NSCLC) patients and head and neck (HN) cancer patients [31]
Summary
Within the TME, myeloid-derived suppressor cells (MDSCs) are a rare group of myeloid cells with immunosuppressive capacities that accumulate in individuals with conditions that include cancer, and sepsis or chronic infection [2]. Early stage MDSCs (E-MDSCs) represent a third progenitor subset that lacks monocytic or and granulocytic markers [6,7,8]. In humans, increased MDSC levels are correlated to poor prognoses for disease outcome, and ablating MDSCs in mice resulted in improved tumor control [9,10,11]. MDSCs are good potential predictors for clinical progression or targets for future immunotherapeutic strategies. We compare isolation mechanisms for murine and human MDSCs, and the current technical limitations.
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