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Common extracellular matrix regulation of myeloid cell activity in the bone marrow and tumor microenvironments

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Abstract

The complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME. Here, we focus on the extracellular matrix (ECM) regulatory activities that, within the TME, actively contribute to many aspects of tumor progression, acting on both tumor and immune cells. Particularly, ECM-mediated regulation of tumor-associated immunosuppression occurs through the modulation of myeloid cell expansion, localization, and functional activities. Such regulation is not limited to the TME but occurs also within the bone marrow, wherein matricellular proteins contribute to the maintenance of specialized hematopoietic stem cell niches thereby regulating their homeostasis as well as the generation and expansion of myeloid cells under both physiological and pathological conditions. Highlighting the commonalities among ECM-myeloid cell interactions in bone marrow and TME, in this review we present a picture in which myeloid cells might sense and respond to ECM modifications, providing different ECM-myeloid cell interfaces that may be useful to define prognostic groups and to tailor therapeutic interventions.

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Abbreviations

AML:

Acute myeloid leukemia

BM:

Bone marrow

DLBCL:

Diffuse large B cell lymphoma

ECM:

Extracellular matrix

EMT:

Epithelial to mesenchymal transition

HSC:

Hematopoietic stem cell

IFNγ:

Interferon gamma

IL:

Interleukin

LAIR:

Leukocyte-associated Ig-like receptor

LOX:

Lysyl-oxidase

MDS:

Myelodisplastic syndrome

MDSC:

Myeloid-derived suppressor cell

NETs:

Neutrophil extracellular traps

OPN:

Osteopontin

PMN:

Polymorphonuclear

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

TAM:

Tumor-associated macrophage

TME:

Tumor microenvironment

TNF:

Tumor necrosis factor

TSP-1:

Thrombospondin-1

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Author notes

  1. Sabina Sangaletti and Claudia Chiodoni have equally contributed to this work.

Authors and Affiliations

  1. Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo, 42, 20133, Milan, Italy

    Sabina Sangaletti, Claudia Chiodoni & Mario P. Colombo

  2. Tumor Immunology Unit, University of Palermo, Palermo, Italy

    Claudio Tripodo

Authors
  1. Sabina Sangaletti
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  2. Claudia Chiodoni
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  3. Claudio Tripodo
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  4. Mario P. Colombo
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Corresponding author

Correspondence to Mario P. Colombo.

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The authors have no conflict of interest to declare.

Funding

This work was supported by Associazione Italiana per la Ricerca sul Cancro (IG 10137 to Mario P. Colombo, MFAG 12810 to Sabina Sangaletti, IG 17261 to Claudia Chiodoni), and the Italian Ministry of Health (GR-2013-02355637 to Sabina Sangaletti).

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Sangaletti, S., Chiodoni, C., Tripodo, C. et al. Common extracellular matrix regulation of myeloid cell activity in the bone marrow and tumor microenvironments. Cancer Immunol Immunother 66, 1059–1067 (2017). https://doi.org/10.1007/s00262-017-2014-y

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