title: Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells.
abstract: 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.
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Facciabene
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Peng
authors.forename: Ian S
authors.initials: IS
authors.lastname: Hagemann
authors.forename: Klara
authors.initials: K
authors.lastname: Balint
authors.forename: Andrea
authors.initials: A
authors.lastname: Barchetti
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054447:Receptors, CCR10 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C414047:CCL28 protein, human; C515706:CCR10 protein, human; C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D054447:Receptors, CCR10; D042461:Vascular Endothelial Growth Factor A