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Front. Immunol. | doi: 10.3389/fimmu.2018.02629

Targeting Macrophage-Recruiting Chemokines as A Novel Therapeutic Strategy to Prevent The Progression of Solid Tumors

  • 1MRC Centre for Reproductive Health (MRC), University of Edinburgh, United Kingdom
  • 2Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom

Solid tumors are initiated by genetic mutations in non-hematopoietic cells and progress into invasive malignant tumors. This tumor progression often culminates in metastatic disease that is largely refractory to current therapeutic modalities and thus dramatically reduces survival of tumor patients. As solid tumors account for more than 80% of cancer-related deaths, it is necessary to develop novel therapeutic strategies to treat the diseases. An attractive strategy is to target macrophages in both primary tumors (known as tumor-associated macrophages (TAMs)) and metastatic tumors (called metastasis-associated macrophages (MAMs)). TAMs and MAMs are abundant in most solid tumors and can promote tumor metastasis. Several studies in various models of solid tumors suggest that the accumulation of TAMs, MAMs, and their progenitor cells is regulated by chemokine ligands released by tumor and stromal cells. Consequently, these macrophage-recruiting chemokines could be potential therapeutic targets to prevent malignant tumor development through disruption of the accumulation of pro-metastatic macrophages. This review will discuss the role of chemokine ligands and their receptors in TAM and MAM accumulation in primary and secondary tumor sites, and finally discuss the therapeutic potential of inhibitors against these macrophage-recruiting chemokines.

Keywords: Cancer, metastasis, Tumor-associated macrophage (TAM), chemokine, antagonist, Immunotharapy

Received: 27 Jul 2018; Accepted: 25 Oct 2018.

Edited by:

Brian A. Zabel, Palo Alto Veterans Institute for Research, United States

Reviewed by:

Jose Miguel Rodriguez Frade, Consejo Superior de Investigaciones Científicas (CSIC), Spain
Paul Proost, Rega Institute for Medical Research, KU Leuven, Belgium
Eric Wilson, Brigham Young University, United States  

Copyright: © 2018 Kitamura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Takanori Kitamura, MRC Centre for Reproductive Health (MRC), University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom, tkitamur@exseed.ed.ac.uk