2013
DOI: 10.1038/onc.2013.121
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Tumor stroma: a complexity dictated by the hypoxic tumor microenvironment

Abstract: A lot of effort has been done to study how cancer cells react to low-oxygen tension, a condition known as hypoxia. Indeed, abnormal and dysfunctional blood vessels in the tumor are incapable to restore oxygenation, therefore perpetuating hypoxia, which, in turn, will fuel tumor progression, metastasis and resistance to antitumor therapies. Nevertheless, how stromal components including blood and lymphatic endothelial cells, pericytes and fibroblasts, as well as hematopoietic cells, respond to low-oxygen tensio… Show more

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Cited by 204 publications
(181 citation statements)
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References 142 publications
(197 reference statements)
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“…Our observation of target cell shifting to late apoptosis through hypoxic NK cell preculture leads us to speculate that oxygen availability during NK cell conditioning can modulate target cell death immunogenicity. This would not withstand hypoxia-mediated immunosuppression through tumor and stroma-derived factors (9,10). In fact, respiratory hyperoxia leads to NK cell-dependent regression of MCA205 pulmonary tumors in mice (72).…”
Section: H (17) and Through Il-15 For H (19)mentioning
confidence: 99%
See 1 more Smart Citation
“…Our observation of target cell shifting to late apoptosis through hypoxic NK cell preculture leads us to speculate that oxygen availability during NK cell conditioning can modulate target cell death immunogenicity. This would not withstand hypoxia-mediated immunosuppression through tumor and stroma-derived factors (9,10). In fact, respiratory hyperoxia leads to NK cell-dependent regression of MCA205 pulmonary tumors in mice (72).…”
Section: H (17) and Through Il-15 For H (19)mentioning
confidence: 99%
“…Therefore, they experience oxygen levels ranging from 5% in venous to 13% in arterial blood and down to 3-2% in healthy tissue and below (hypoxia) in the bone marrow, the lymphatic system, at sites of inflammation, and in the tumor microenvironment (3)(4)(5)(6)(7)(8)(9). Tumor hypoxia is thought to support tumor escape from NK cell-mediated cytotoxicity (9,10). In vitro, promotion of NK cell-mediated cell killing by interleukin-2 (IL-2) was reported to be reduced after 96 h at 1% O 2 compared with 20% O 2 , although antibody-dependent cellular cytotoxicity was not affected (11).…”
Section: Natural Killer (Nk)mentioning
confidence: 99%
“…Neoplastic cells recruit and incorporate adjacent or distant healthy host cells, such as bone marrow-derived cells (BMDCs) for support and essential nutrients (2). Neoplastic cells also recruit fibroblasts, mesenchymal cells, macrophages, endothelial cells, pericytes, hematopoietic cells and extracellular matrix (3), all of which together with other components constitute the tumor microenvironment (TME) (1). Tumor host cells exchange cytokines (such as IL-6, GM-CSF and IL-4), extracellular matrix proteins, enzymes and vesicles in distinct sizes, which promote tumor development, progression and metastases (4,5).…”
Section: Introductionmentioning
confidence: 99%
“…This in turn leads to hypoxia and lowering of the microenvironment pH, which further promotes tumor progression. At the same time hypo-perfusion and hypoxia compromise normal immune response, thus rendering the tumor impervious to the immune system [11,12] with an invasive and metastatic phenotype [13]. As expected, reduced blood supply also interferes with effective drug delivery to the tumor [9].…”
Section: Causes Of Insufficient Drug Delivery To Tumorsmentioning
confidence: 75%