The irradiated tumor microenvironment: role of tumor-associated macrophages in vascular recovery
- 1Department of Medical Oncology, Stanford University School of Medicine, Stanford, CA, USA
- 2Division of Cancer and Radiation Biology, Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, USA
Radiotherapy is an important modality used in the treatment of more than 50% of cancer patients in the US. However, despite sophisticated techniques for radiation delivery as well as the combination of radiation with chemotherapy, tumors can recur. Thus, any method of improving the local control of the primary tumor by radiotherapy would produce a major improvement in the curability of cancer patients. One of the challenges in the field is to understand how the tumor vasculature can regrow after radiation in order to support tumor recurrence, as it is unlikely that any of the endothelial cells within the tumor could survive the doses given in a typical radiotherapy regimen. There is now considerable evidence from both preclinical and clinical studies that the tumor vasculature can be restored following radiotherapy from an influx of circulating cells consisting primarily of bone marrow derived monocytes and macrophages. The radiation-induced influx of bone marrow derived cells (BMDCs) into tumors can be prevented through the blockade of various cytokine pathways and such strategies can inhibit tumor recurrence. However, the post-radiation interactions between surviving tumor cells, recruited immune cells, and the remaining stroma remain poorly defined. While prior studies have described the monocyte/macrophage inflammatory response within normal tissues and in the tumor microenvironment, less is known about this response with respect to a tumor after radiation therapy. The goal of this review is to summarize existing research studies to provide an understanding of how the myelomonocytic lineage may influence vascular recovery within the irradiated tumor microenvironment.
Keywords: radiation, macrophages, vasculogenesis, angiogenesis, blood vessels, tumor growth
Citation: Russell JS and Brown JM (2013) The irradiated tumor microenvironment: role of tumor-associated macrophages in vascular recovery. Front. Physiol. 4:157. doi: 10.3389/fphys.2013.00157
Received: 27 March 2013; Accepted: 11 June 2013;
Published online: 17 July 2013.
Edited by:Michal A. Rahat, Technion - Israel Institute for Technology, Israel
Reviewed by:Seth B. Coffelt, Netherlands Cancer Institute, Netherlands
Lily Wu, University of California, Los Angeles, USA
Copyright © 2013 Russell and Brown. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: J. Martin Brown, Division of Cancer and Radiation Biology, Department of Radiation Oncology, Stanford University School of Medicine, 1050A Arastradero Rd., Rm A246, Palo Alto, Stanford, CA 94304-1334, USA e-mail: firstname.lastname@example.org