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The role of CCR5 in directing the mobilization and biological function of CD11b+Gr1+Ly6Clow polymorphonuclear myeloid cells in cancer

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Abstract

Bone marrow (BM) cells of the hematopoietic system, also known as BM-derived leukocytes (BMD), are mobilized from the BM to the blood and then colonize tumor sites. These cells then become key players in either promoting or regulating the development and progression of tumors. Among the cells that suppress anti-tumor immunity are regulatory T cells (Tregs), tumor-associated macrophages (TAMS) and myeloid-derived suppressor cells (MDSC). MDSC comprise CD11b+Gr1+Ly6Clow polymorphonuclear myeloid cells (PMN-MDSC), and CD11b+Gr1+Ly6Chigh monocytic myeloid cells (Mo-MDSC). Several studies including ours have identified the CCR2–CCL2 axis as the key driver of the mobilization of monocytic cells from the BM to the blood and later their colonization at the tumor site. The current review focuses on the mechanisms by which PMN-MDSC are mobilized from the BM to the blood and later to the tumor site, and their clinical implications.

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Abbreviations

Arg1:

Arginase 1

BM:

Bone marrow

BMD:

Bone marrow derived

CTLA-4:

Cytotoxic T-lymphocyte-associated antigen 4

DKFZ:

Deutsche Krebsforschungszentrum (German Cancer Research Center)

ECM:

Extracellular matrix

MDSCs:

Myeloid-derived suppressor cells

Mo-MDSCs:

Monocytic myeloid-derived suppressor cells

MOST:

Ministry of Science, Technology and Space of Israel

MSCs:

Mesenchymal stem cells

NK:

Natural killer cells

PMN-MDSCs:

Polymorphonuclear myeloid-derived suppressor cells

Tr1:

T-regulatory 1 cells

TAMs:

Tumor-associated macrophages

TME:

Tumor microenvironment

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Funding

The studies of Nathan Karin and his group described in the current review were funded by the co-operational research program of the Deutsche Krebsforschungszentrum (German Cancer Research Center) (DKFZ), Heidelberg, Germany, with the Ministry of Science, Technology & Space (MOST) of Israel (DKFZ—MOST), Grant #CA157, the Israel Cancer Research fund (ICRF) Grant #171961-PG, and Israel Science Foundation (ISF) Grant # 630/15.

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Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine, Technion, P.O.B. 9697, 31096, Haifa, Israel

    Nathan Karin & Hila Razon

Authors
  1. Nathan Karin
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  2. Hila Razon
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Contributions

NK wrote the review and HR participated in discussions and in editing the review.

Corresponding author

Correspondence to Nathan Karin.

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There is no conflict of interest.

Ethical approval and ethical standards

All animal experiments were conducted according to the Technion ethic committee guidelines, Technion animal experimentation protocol no. IL-128-12-2012 and protocol no. IL-062-06-2015.

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Karin, N., Razon, H. The role of CCR5 in directing the mobilization and biological function of CD11b+Gr1+Ly6Clow polymorphonuclear myeloid cells in cancer. Cancer Immunol Immunother 67, 1949–1953 (2018). https://doi.org/10.1007/s00262-018-2245-6

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  • DOI: https://doi.org/10.1007/s00262-018-2245-6

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