Myeloid-derived suppressor cells (MDSCs) in patients with solid tumors: considerations for granulocyte colony-stimulating factor treatment
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Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor escape from host immune surveillance and to cancer progression by production of tumor-promoting soluble factors. Granulocyte colony-stimulating factor (G-CSF) is a principle cytokine controlling granulocyte number. Recombinant human G-CSF (rhG-CSF) has become the main therapeutic agent for the treatment of neutropenia and prophylaxis of febrile neutropenia in cancer patients. However, we show here that rhG-CSF triggers accumulation of granulocytic and monocytic subsets. Consequently, we discuss the pharmacological use of granulopoiesis stimulating factors not only in the context of febrile neutropenia but also from the perspective of MDSC-dependent and MDSC-independent mechanisms of immunosuppression and cancer angiogenesis.
KeywordsMyeloid-derived suppressor cells Granulocyte colony-stimulating factor Cancer Prophylaxis of febrile neutropenia CITIM 2017
American Society of Clinical Oncology
Basic fibroblast growth factor
CCAAT/enhancer-binding protein beta
Compensatory anti-inflammatory response syndrome
Danger-associated molecular pattern
European Medicines Agency
Early myeloid-derived suppressor cell
Food and Drug Administration
High-mobility group box 1
Monocytic myeloid-derived suppressor cell
Pathogen-associated molecular pattern
Platelet-derived growth factor
Prostaglandin E 2
Polymorphonuclear myeloid-derived suppressor cell
Recombinant human granulocyte colony-stimulating factor
Reactive oxygen species
KP performed or supervised laboratory testing, contributed to data interpretation, prepared figures, and drafted the manuscript. BB referred patients and drafted the manuscript. RD contributed to data interpretation and drafted the manuscript. DV drafted and edited the manuscript. LZ-D conceived of the presented idea, designed the experiment and laboratory testing, and drafted and finalized the manuscript. All authors discussed the results and contributed to the final manuscript.
The work was supported by the Czech Ministry of Health (projects AZV 16-31966A and DRO 00209805) and the Czech Ministry of Education, Youth and Sports (projects LO1413, LM2015089, and LM2015090).
Compliance with ethical standards
For pediatric patients treated by anti-cancer DC vaccines, academic clinical trial (EudraCT: 2014-003388-39) was approved by Czech national authority (State Institute for Drug Control).
For adult cancer patients, the study was approved by Ethical Board of Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Conflict of interest
The authors declare that they have no conflicts of interest.
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