Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T reg cells

Andrea Facciabene, Xiaohui Peng, Ian S. Hagemann, Klara Balint, Andrea Barchetti, Li Ping Wang, Phyllis A. Gimotty, C. Blake Gilks, Priti Lal, Lin Zhang, George Coukos

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600 Scopus citations


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.

Original languageEnglish
Pages (from-to)226-230
Number of pages5
Issue number7355
StatePublished - Jul 14 2011
Externally publishedYes

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    Facciabene, A., Peng, X., Hagemann, I. S., Balint, K., Barchetti, A., Wang, L. P., Gimotty, P. A., Gilks, C. B., Lal, P., Zhang, L., & Coukos, G. (2011). Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T reg cells. Nature, 475(7355), 226-230. https://doi.org/10.1038/nature10169