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Cancer Immunology, Immunotherapy

, Volume 66, Issue 8, pp 1025–1036 | Cite as

Tumor-associated myeloid cells as guiding forces of cancer cell stemness

  • Antonio SicaEmail author
  • Chiara Porta
  • Alberto Amadori
  • Anna Pastò
Focussed Research Review

Abstract

Due to their ability to differentiate into various cell types and to support tissue regeneration, stem cells simultaneously became the holy grail of regenerative medicine and the evil obstacle in cancer therapy. Several studies have investigated niche-related conditions that favor stemness properties and increasingly emphasized their association with an inflammatory environment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are major orchestrators of cancer-related inflammation, able to dynamically express different polarized inflammatory programs that promote tumor outgrowth, including tumor angiogenesis, immunosuppression, tissue remodeling and metastasis formation. In addition, these myeloid populations support cancer cell stemness, favoring tumor maintenance and progression, as well as resistance to anticancer treatments. Here, we discuss inflammatory circuits and molecules expressed by TAMs and MDSCs as guiding forces of cancer cell stemness.

Keywords

Cancer stem cells Tumor-associated macrophages Regulatory myeloid suppressor cells Myeloid-derived suppressor cells Inflammation 

Abbreviations

ALDH

Aldehyde dehydrogenases

CCR2

C–C chemokine receptor type 2

CSCs

Cancer stem cells

CtBP2

C-terminal-binding protein 2

EMT

Epithelial–mesenchymal transition

EOC

Epithelial ovarian cancer

HCC

Hepatocellular carcinoma

HIF-1α

Hypoxia-inducible factor-1α

IL-1Ra

Interleukin-1 receptor antagonist

ISG15

Interferon-stimulated gene 15

MDR1/2

Multidrug resistance protein 1/2

MDSCs

Myeloid-derived suppressor cells

MFG-E8

Milk fat globule-epidermal growth factor-VIII

MSCs

Mesenchymal stem cells

OXPHOS

Oxidative phosphorylation

PDAC

Pancreatic ductal adenocarcinoma

ROS

Reactive oxygen species

SCF

Stem cell factor

TAF

Tumor-associated fibroblast

TAMs

Tumor-associated macrophages

TIC

Tumor-initiating cell

TME

Tumor microenvironment

Notes

Acknowledgements

This work was supported by Associazione Italiana Ricerca sul Cancro (AIRC), project #15585, #14032 Italy; Fondazione Cariplo, Italy; Ministero Università Ricerca (MIUR), Italy, (Grant Numbers: RBAU01PTYW; RBNE01XHB2_002; RBAP11H2R9_005); Ministero della Salute (GR-2011-02349580); Istituto Oncologico Veneto 5x1000 grant.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Antonio Sica
    • 1
    • 2
    Email author
  • Chiara Porta
    • 1
  • Alberto Amadori
    • 3
    • 4
  • Anna Pastò
    • 4
  1. 1.Department of Pharmaceutical SciencesUniversità del Piemonte Orientale “Amedeo Avogadro”NovaraItaly
  2. 2.Humanitas Clinical and Research CenterRozzano, MilanItaly
  3. 3.Department of Surgery, Oncology and GastroenterologyUniversity of PadovaPaduaItaly
  4. 4.Istituto Oncologico Veneto IOV-IRCCSPaduaItaly

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