IFN-{gamma}+ CD8+ T Lymphocytes: Possible Link Between Immune and Radiation Responses in Tumor-Relevant Hypoxia
- Radiotherapie, Oncologisch Centrum, UZ Brussel, Brussels (Belgium)
- Cancer Research Unit, Vrije Universiteit Brussel, Brussels (Belgium)
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 immunosorbent 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.
- OSTI ID:
- 21124300
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 71, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2008.03.014; PII: S0360-3016(08)00481-1; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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