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The irradiated tumor microenvironment: role of tumor-associated macrophages in vascular recovery.

Russell JS, Brown JM - Front Physiol (2013)

Bottom Line: Radiotherapy is an important modality used in the treatment of more than 50% of cancer patients in the US.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Stanford University School of Medicine Stanford, CA, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Representation ofthe microenvironment of pre- and postirradiated tumors. The post-irradiated tumor has increased levels of hypoxia, upregulated HIF 1/2 signaling, and expression of a diverse spectrum of cytokines as well as a greater recruitment and influx of bone marrow derived TAMs. TEMs commonly associate with the vasculature, while CD68+ TAMs frequently localize to areas of severe hypoxia.
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Figure 1: Representation ofthe microenvironment of pre- and postirradiated tumors. The post-irradiated tumor has increased levels of hypoxia, upregulated HIF 1/2 signaling, and expression of a diverse spectrum of cytokines as well as a greater recruitment and influx of bone marrow derived TAMs. TEMs commonly associate with the vasculature, while CD68+ TAMs frequently localize to areas of severe hypoxia.

Mentions: The tumor microenvironment is often transiently or chronically in a state of low oxygen tension (Vaupel and Mayer, 2007). To survive in a hypoxic environment, tumors must establish a functional vascular network (See Figure 1). Tumors frequently adapt to hypoxia by preventing the degradation of hypoxia-induced transcription factor complexes (i.e., HIF1 and HIF2) resulting in their stabilization and subsequent transcription of genes that promote tumor survival, including proangiogenic cytokines (Giaccia et al., 2004; Keith et al., 2012). Using primary human macrophages, Fang et al. demonstrated that HIF1 and HIF2 co-regulate many hypoxia-related genes; however, by using siRNA specific knockdown studies of HIF1 and HIF2, they found that each of these genes can target certain hypoxia-associated genes independently (Fang et al., 2009).


The irradiated tumor microenvironment: role of tumor-associated macrophages in vascular recovery.

Russell JS, Brown JM - Front Physiol (2013)

Representation ofthe microenvironment of pre- and postirradiated tumors. The post-irradiated tumor has increased levels of hypoxia, upregulated HIF 1/2 signaling, and expression of a diverse spectrum of cytokines as well as a greater recruitment and influx of bone marrow derived TAMs. TEMs commonly associate with the vasculature, while CD68+ TAMs frequently localize to areas of severe hypoxia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3713331&req=5

Figure 1: Representation ofthe microenvironment of pre- and postirradiated tumors. The post-irradiated tumor has increased levels of hypoxia, upregulated HIF 1/2 signaling, and expression of a diverse spectrum of cytokines as well as a greater recruitment and influx of bone marrow derived TAMs. TEMs commonly associate with the vasculature, while CD68+ TAMs frequently localize to areas of severe hypoxia.
Mentions: The tumor microenvironment is often transiently or chronically in a state of low oxygen tension (Vaupel and Mayer, 2007). To survive in a hypoxic environment, tumors must establish a functional vascular network (See Figure 1). Tumors frequently adapt to hypoxia by preventing the degradation of hypoxia-induced transcription factor complexes (i.e., HIF1 and HIF2) resulting in their stabilization and subsequent transcription of genes that promote tumor survival, including proangiogenic cytokines (Giaccia et al., 2004; Keith et al., 2012). Using primary human macrophages, Fang et al. demonstrated that HIF1 and HIF2 co-regulate many hypoxia-related genes; however, by using siRNA specific knockdown studies of HIF1 and HIF2, they found that each of these genes can target certain hypoxia-associated genes independently (Fang et al., 2009).

Bottom Line: Radiotherapy is an important modality used in the treatment of more than 50% of cancer patients in the US.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Stanford University School of Medicine Stanford, CA, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus