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Title
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IFN-gamma+CD8+ T lymphocytes: Possible link between immune and radiation responses in tumor-relevant hypoxia
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Author
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Abstract
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| Activated T lymphocytes are known to kill tumor cells by triggering cytolytic mechanisms; however, their ability to enhance radiation responses remains unclear. This study examined the radiosensitizing potential of mouse CD8+ T cells, obtained by T-cell-tailored expansion and immunomagnetic purification. Activated CD8+ T cells displayed an interferon (IFN)-gamma+ phenotype and enhanced by 1.8-fold the radiosensitivity of EMT-6 tumor cells in 1% oxygen, which modeled tumor-relevant hypoxia. Radiosensitization was counteracted by neutralizing IFN-gamma or by blocking the inducible isoform of nitric oxide synthase, thus delineating the immune-tumor cell interaction through the IFN-gamma secretion pathway. Reverse transcriptase-polymerase chain reaction, enzyme-linked immuno-sorbent assay, and fluorescence-activated cell sorter data in agreement detected downregulation of the IFN-gamma gene by hypoxia, which caused IFN-gamma deficiency next to radioresistance. Therefore, immune and radiation responses are likely to be allied in the hypoxic tumor microenvironment, and CD8+ T cells may bridge immunostimulatory and radiosensitizing strategies. (c) 2008 Elsevier Inc. |
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Language
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English
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Source (journal)
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International journal of radiation oncology, biology, physics. - Bedford
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Publication
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Bedford
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2008
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ISSN
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0360-3016
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DOI
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10.1016/J.IJROBP.2008.03.014
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Volume/pages
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71
:3
(2008)
, p. 647-651
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ISI
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000256572400001
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Full text (Publisher's DOI)
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