Article: article from journal or magazin.
Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells.
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Although immune mechanisms can suppress tumour growth, tumours establish potent, overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms. Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth.
Animals, Cell Hypoxia/genetics, Cell Line, Tumor, Chemokines, CC/genetics, Chemokines, CC/metabolism, Culture Media, Conditioned/pharmacology, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Humans, Immune Tolerance/immunology, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, Ovarian Neoplasms/blood supply, Ovarian Neoplasms/immunology, Receptors, CCR10/metabolism, T-Lymphocytes, Regulatory/drug effects, T-Lymphocytes, Regulatory/immunology, Vascular Endothelial Growth Factor A/metabolism, Vascular Endothelial Growth Factor A/secretion
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