MDSCs expand under pathologic conditions such as chronic infection and cancer, as a result of altered haematopoiesis.
Tumor cell lines overexpress colony-stimulating factors (G-CSF and GM-CSF) and IL6, which promote development of MDSCs that have immune suppressive function in vivo.
[11] MDSCs migrate as immature cells from the bone marrow to peripheral tissues (or tumors), where they differentiate into mature macrophages, dendritic cells, and neutrophils without suppressive phenotypes under homeostatic conditions, but become polarized when exposed to pro-inflammatory compounds, chemokines, and cytokines.
In fact, they are used in research to develop therapeutic strategies against both autoimmune diseases and exacerbate inflammation, which has especial interest in the central nervous system).
[13][14][15] However, a recent research of the University of Salamanca has demonstrated that immature myeloid cells (IMCs), the precursors of MDSCs, have also potential immunosuppressive activity under pathological conditions.
They application in an intracranial surgery almost completely prevented the impairments caused by this procedure in mice, probably by the modulation of the inflammatory patterns.
[18] In this sense, IMCs have a direct pre-clinical application to minimize the secondary effects inherent to every single intracranial surgery, especially in a diseased environment.
MDSCs derive from bone marrow precursors usually as the result of a perturbed myeloipoiesis caused by different pathologies.
In cancer patients, growing tumors secrete a variety of cytokines and other molecules which are key signals involved in the generation of MDSC.
Tumor cell lines overexpressing colony stimulating factors (e.g. G-CSF and GM-CSF) have long been used in vivo models of MDSC generation.
[2][19] The myeloid-differentiation cytokine GM-CSF is a key factor in MDSC production from bone marrow,[20][unreliable medical source?]
and it has been shown that the c/EBPβ transcription factor plays a key role in the generation of in vitro bone marrow-derived and in vivo tumor-induced MDSC.
While monocyte and neutrophil differentiation pathways within the bone marrow are antagonistic and dependent on the relative expression of IRF8 and c/EBP transcription factors (and hence there is not a direct precursor-progeny link between these two myeloid cell types), this seems not to be the case for MDSCs.
The combination of LPS and IFNg treatment of bone marrow-derived MDSCs limits DC formation and improves MDSC suppressive action.
[2] In 2015, MDSCs were compared to immunogenic myeloid cells highlighting a group of core signaling pathways that control pro-carcinogenic MDSC functions.
As of May 2018[update] there are no FDA approved drugs developed to target MDSCs but experimental INB03 has entered early clinical trials.
[33][34] In a Phase 1b clinical trial of GR-MD-02 developed by Galectin Therapeutics, investigators observed a significant decrease in the frequency of suppressive myeloid-derived suppressor cells following treatment in responding melanoma patients.