On the origin of myeloid-derived suppressor cells

Abstract

Myeloid-derived suppressor cells (MDSCs) have a strong immunosuppressive character that allows them to regulate immune responses and hinder overt inflammatory responses. In cancer, this leads to tumor immune evasion and disease progression. MDSCs come in at least two forms: monocytic (Mo-MDSCs) and granulocytic (G-MDSCs). The classical definition of MDSCs as immature myeloid cells blocked from differentiating has been challenged by recent studies suggesting that Mo-MDSCs and G-MDSCs may represent monocytes and granulocytes that have acquired immunosuppressive properties. The molecular mechanism behind their generation and their true origins are now widely debated. In this review we discuss the different proposed mechanisms of the generation of both types of MDSCs, with a special focus on human MDSCs in cancer.

Myeloid-derived suppressor cells in gliomas

“…Additionally, a more immature subset of human MDSCs characterised by the absence of staining for the lineage cocktail (CD3 – , CD14 – , CD15 – , CD19 – , CD56 – ), HLA-DR − , and expression of the common myeloid markers CD33 and CD11b has been identified as an “early stage” e-MDSC, defined. Using a multi-colour staining protocol and taking into account all the reported myeloid subsets endowed with a suppressive activity, a recent study discriminated six human MDSC phenotypes: MDSC1 (CD14 + IL-4Rα + ), MDSC2 (CD15 + IL-4Rα + ), MDSC3 (Lineage − HLA-DR − CD33 + ), MDSC4 (CD14 + HLA-DR low/− ), MDSC5 (CD11b + CD14 − CD15 + ), and MDSC6 (CD15 + FSC low SSC high ) (Table 1) [8–10]. The detection of different human MDSC phenotypes highlighted the lack of standardisation in this area and led to the establishment of a human MDSC proficiency panel according to the guidance of the Association of Cancer Immunotherapy (CIMT) Immunoguiding Program in order to promote the standardisation of MDSC immunophenotyping across different groups.…”

“…The concept of block in differentiation states that immature myeloid cells are arrested in their immature phase by inflammatory mediators such as S100A8, S100A9, VEGF, IL-10, and COX-2/prostaglandin PGE2 [21, 22]. The classical definition of MDSCs as immature myeloid cells blocked from terminal differentiation has been challenged by recent studies suggesting that M-MDSCs and PMN-MDSCs may represent monocytes and granulocytes that have acquired immunosuppressive properties [10]. Both emergency myelopoiesis and block in differentiation are linked to an abnormal and persistent activation of STAT3.…”

“…MDSC percentages increase under pathological conditions, as a result of signals released by tumour cells or chronic inflammation [24]. Emerging evidence suggests that M-MDSCs are generated by reprogramming of monocytes into M-MDSCs, whereas PMN-MDSCs might be generated from neutrophils through the activation of immature or mature granulocytes and represent different stages of activation [10]. …”

Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study

“…Several studies have shown that the neutrophil‐to‐lymphocyte ratio (NLR) and the absolute neutrophil count (ANC) in the blood can predict the efficacy of PD‐1 inhibitors in patients with NSCLC . NLR and ANC have also been reported to reflect the number of circulating myeloid‐derived suppressor cells (MDSCs) and tumor‐associated neutrophils, which inhibit the function of antitumor T cells . The immunosuppressive status in the tumor microenvironment could be monitored using the dynamics of NLR and ANC.…”

Hematopoietic stem cell-derived myeloid and plasmacytoid DC-based vaccines are highly potent inducers of tumor-reactive T cell and NK cell responsesex vivo

“…Within the HLA-DR negative fraction, we could identify a population of cells double positive for CD15 and CD11b (Fig. S7D–E), a phenotype associated with myeloid-derived suppressor cells 56 . Since we observed these cells primarily in the long (i.e., >19 d) G4 cultures (7–18% of total cultured cells), we favor the shorter culture procedure (i.e., <16 d), where the frequency of HLA-DR − CD15 + CD11b + cells was <4% out of total cultured cells.…”