Complexity and challenges in defining myeloid-derived suppressor cells - PubMed (original) (raw)

Review

Complexity and challenges in defining myeloid-derived suppressor cells

Vera Damuzzo et al. Cytometry B Clin Cytom. 2015 Mar.

Abstract

Study of myeloid cells endowed with suppressive activity is an active field of research which has particular importance in cancer, in view of the negative regulatory capacity of these cells to the host's immune response. The expansion of these cells, called myeloid-derived suppressor cells (MDSCs), has been documented in many models of tumor-bearing mice and in patients with tumors of various origin, and their presence is associated with disease progression and reduced survival. For this reason, monitoring this type of cell expansion is of clinical importance, and flow cytometry is the technique of choice for their identification. Over the years, it has been demonstrated that MDSCs comprise a group of immature myeloid cells belonging both to monocytic and granulocytic lineages, with several stages of differentiation; their occurrence depends on tumor-derived soluble factors, which guide their expansion and determine their block of differentiation. Because of their heterogeneous composition, accurate phenotyping of these cells requires a multicolor approach, so that the expansion of all MDSC subsets can be appreciated. This review article focuses on identifying MDSCs and discusses problems associated with phenotyping circulating and tumor-associated MDSCs in humans and in mouse models.

Keywords: MDSC; immune suppression; immunology; immunophenotyping; oncology.

© 2014 International Clinical Cytometry Society.

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Figures

Figure 1

Figure 1

Subsets of mouse MDSCs. Dot plots showing distribution of Mo-MDSCs (Ly6ChighLY6G−) and PMN-MDSCs (LY6CintLY6G+) found in bone marrow (A), blood (B), spleen (C), lymph nodes (D), and tumor mass (E) of mice challenged with MCA203 fibrosarcoma. Comparison with MDSCs found in tumor mass of mice bearing MN/MCA1 osteosarcoma shown in (F). Analysis performed on CD11b+ cells, after exclusion of cell doublets and dead cells.

Figure 2

Figure 2

Main subsets of human MDSCs. PBMCs from healthy donors stained with 8-color panel to identify the seven main subsets of circulating human MDSCs (A–G). A morphological gate including mononuclear cells (based on FSC and SSC properties) and exclusion of doublets (based on SSC-A vs. SSC-H and FSC-A vs. FSC-H parameters) and dead cells (cells negative for the Live/Dead dye) were applied before gating for MDSC subsets. Figure shows three subsets of monocytic MDSCs: CD14+/IL4Rα+ (A) (28), CD14+/HLA-DRlow/− (C) (56), CD15−/CD14+/CD33high/HLA-DRlow/− (F) (66); three of granulocytic MDSCs: CD15+/IL4Rα+ (B) (28), CD14−/CD15+/CD11b+ (D) (51), CD15high/FSClow/SSChigh (E) (50) and one of immature MDSC: Lin−/HLA-DR− /CD33+/CD11b+ (G) (61,63).

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