期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 41, 期 7, 页码 1843-1849出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201040868
关键词
Reactive nitrogen species; T-cell activation; Tumor microenvironment
类别
资金
- Italian Ministry of Health
- Italian Association for Cancer Research (AIRC)
- MIUR/COFIN
- Association for International Cancer Research (AICR) [08-0518, 09-0597]
- Istituto Superiore Sanita-Alleanza Contro il Cancro [ACC8]
- US Army Medical Research and Materiel Command
Previous studies have suggested that T-lymphocyte dysfunction might be attributable to nitrative stress induced by reactive nitrogen species (RNS). In this manuscript, we explored this hypothesis and provided a direct demonstration of the inhibitory effects of RNS on human T-cell signaling, activation, and migration. We found that short exposure of human T cells to RNS induced tyrosine phosphorylation of several proteins, including the CD3 zeta chain of the TCR complex, and release of Ca(2+) from intracellular stores. When the exposure to RNS was prolonged, T cells became refractory to stimulation, downregulated membrane receptors such as CD4, CD8, and chemokine receptors, and lost their ability to migrate in response to chemokines. Since substantial protein nitration, a hallmark of nitrative stress, was observed in various human cancers, intratumoral generation of RNS might represent a relevant mechanism for tumor evasion from immune surveillance.
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