Cancer Immunology, Immunotherapy

, Volume 66, Issue 8, pp 1059–1067 | Cite as

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

  • Sabina Sangaletti
  • Claudia Chiodoni
  • Claudio Tripodo
  • Mario P. Colombo
Focussed Research Review

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.

Keywords

Regulatory myeloid suppressor cells SPARC Tumor microenvironment Bone marrow niche Extracellular matrix 

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

Notes

Compliance with ethical standards

Conflict of interest

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Sabina Sangaletti
    • 1
  • Claudia Chiodoni
    • 1
  • Claudio Tripodo
    • 2
  • Mario P. Colombo
    • 1
  1. 1.Molecular Immunology Unit, Department of Experimental Oncology and Molecular MedicineFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  2. 2.Tumor Immunology UnitUniversity of PalermoPalermoItaly

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