History of myeloid-derived suppressor cells

Abstract

Tumour-induced granulocytic hyperplasia is associated with tumour vasculogenesis and escape from immunity via T cell suppression. Initially, these myeloid cells were identified as granulocytes or monocytes; however, recent studies have revealed that this hyperplasia is associated with populations of multipotent progenitor cells that have been identified as myeloid-derived suppressor cells (MDSCs). The study of MDSCs has provided a wealth of information regarding tumour pathobiology, has extended our understanding of neoplastic progression and has modified our approaches to immune adjuvant therapy. In this Timeline article, we discuss the history of MDSCs, their influence on tumour progression and metastasis, and the crosstalk between tumour cells, MDSCs and the host macroenvironment.

Figure 1. Timeline: Historical Progression of MDSCs in the Literature

Antibody (Ab); a disintegrin and metallopeptidase domain-containing protein10 (ADAM10); all-trans retinoic acid (ATRA); bombina variagata peptide 8 (BV8); colony stimulating factor (CSF); FMS-like tyrosine kinase 3 (FLT3); granulocyte colony stimulating factor (G-CSF); granulocyte-macrophage colony stimulating factor (GM-CSF); graft versus host disease (GVHD); hypoxia inducible factor 1 alpha (HIF-1α); head and neck squamous cell carcinoma (HNSCC); knock out (KO); macrophage colony stimulating factor (M-CSF); myeloid-derived suppressor cell (MDSC); micro RNA 494 (miRNA-494); mixed lymphocyte reaction (MLR): myeloid differentiation primary response 88 (MYd88); nuclear factor kappa beta (NF-Kβ); nitric oxide (NO): nitric oxide synthase 2 (NOS2); natural suppressor (NS); phosphodiesterase type 5 (PDE5); renal cell carcinoma (RCC); signal transducer and activator of transcription 3 (STAT3); tumour bearing (TB); and, vascular endothelial growth factor (VEGF).

Figure 1. Timeline: Historical Progression of MDSCs in the Literature

Antibody (Ab); a disintegrin and metallopeptidase domain-containing protein10 (ADAM10); all-trans retinoic acid (ATRA); bombina variagata peptide 8 (BV8); colony stimulating factor (CSF); FMS-like tyrosine kinase 3 (FLT3); granulocyte colony stimulating factor (G-CSF); granulocyte-macrophage colony stimulating factor (GM-CSF); graft versus host disease (GVHD); hypoxia inducible factor 1 alpha (HIF-1α); head and neck squamous cell carcinoma (HNSCC); knock out (KO); macrophage colony stimulating factor (M-CSF); myeloid-derived suppressor cell (MDSC); micro RNA 494 (miRNA-494); mixed lymphocyte reaction (MLR): myeloid differentiation primary response 88 (MYd88); nuclear factor kappa beta (NF-Kβ); nitric oxide (NO): nitric oxide synthase 2 (NOS2); natural suppressor (NS); phosphodiesterase type 5 (PDE5); renal cell carcinoma (RCC); signal transducer and activator of transcription 3 (STAT3); tumour bearing (TB); and, vascular endothelial growth factor (VEGF).

Figure 2. The role of MDSCs in the process of cancer progression and metastasis

The process of cancer metastasis consists of sequential, interlinked, and selective steps with some stochastic elements. The outcome of each step is influenced by the interaction of metastatic cellular subpopulations with homeostatic factors and cells. Each step of the metastatic cascade is potentially rate limiting such that failure of a tumour cell to complete any step effectively impedes that portion of the process. Therefore, the formation of clinically relevant metastases represents the survival and growth of selected subpopulations of cells that preexist in primary tumours. The interactions between MDSCs and tumour cells during tumour progression and metastasis are highlighted. The role of tumour cells is indicated by green text, and those of MDSCs and other myeloid cells are indicated in red.