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Myeloid-derived suppressor cells (MDSCs) in patients with solid tumors: considerations for granulocyte colony-stimulating factor treatment

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Abstract

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.

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Abbreviations

ASCO:

American Society of Clinical Oncology

ATRA:

All-trans-retinoic acid

bFGF:

Basic fibroblast growth factor

C/EBPβ:

CCAAT/enhancer-binding protein beta

CARS:

Compensatory anti-inflammatory response syndrome

CRP:

C-reactive protein

CSF:

Colony-stimulating factor

DAMP:

Danger-associated molecular pattern

DC:

Dendritic cell

EMA:

European Medicines Agency

e-MDSC:

Early myeloid-derived suppressor cell

FDA:

Food and Drug Administration

FN:

Febrile neutropenia

HMGB1:

High-mobility group box 1

IRF:

Interferon-regulatory factor

M-MDSC:

Monocytic myeloid-derived suppressor cell

MMP:

Matrix metallopeptidase

PAMP:

Pathogen-associated molecular pattern

PDGF:

Platelet-derived growth factor

PEG:

Polyethylene glycol

PGE2:

Prostaglandin E 2

PMN-MDSC:

Polymorphonuclear myeloid-derived suppressor cell

rhG-CSF:

Recombinant human granulocyte colony-stimulating factor

ROS:

Reactive oxygen species

TAM:

Tumor-associated macrophage

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Funding

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).

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic

    Katerina Pilatova, Dalibor Valik & Lenka Zdrazilova-Dubska

  2. RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    Katerina Pilatova, Beatrix Bencsikova, Regina Demlova, Dalibor Valik & Lenka Zdrazilova-Dubska

  3. Department of Pharmacology, Medical Faculty, Masaryk University, Brno, Czech Republic

    Katerina Pilatova, Regina Demlova, Dalibor Valik & Lenka Zdrazilova-Dubska

  4. Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    Beatrix Bencsikova

  5. Clinical Trial Unit, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    Regina Demlova

Authors
  1. Katerina Pilatova
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  2. Beatrix Bencsikova
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  3. Regina Demlova
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  4. Dalibor Valik
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  5. Lenka Zdrazilova-Dubska
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Contributions

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.

Corresponding author

Correspondence to Lenka Zdrazilova-Dubska.

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Ethical approval

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).

Ethical standards

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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Pilatova, K., Bencsikova, B., Demlova, R. et al. Myeloid-derived suppressor cells (MDSCs) in patients with solid tumors: considerations for granulocyte colony-stimulating factor treatment. Cancer Immunol Immunother 67, 1919–1929 (2018). https://doi.org/10.1007/s00262-018-2166-4

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