Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-04

AUTHORS

Max Yan, Nicholas Jene, David Byrne, Ewan KA Millar, Sandra A O'Toole, Catriona M McNeil, Gaynor J Bates, Adrian L Harris, Alison H Banham, Robert L Sutherland, Stephen B Fox

ABSTRACT

INTRODUCTION: Basal-like breast cancers behave more aggressively despite the presence of a dense lymphoid infiltrate. We hypothesised that immune suppression in this subtype may be due to T regulatory cells (Treg) recruitment driven by hypoxia-induced up-regulation of CXCR4 in Treg. METHODS: Immunoperoxidase staining for FOXP3 and CXCL12 was performed on tissue microarrays from 491 breast cancers. The hypoxia-associated marker carbonic anhydrase IX (CA9) and double FOXP3/CXCR4 staining were performed on sections from a subset of these cancers including 10 basal-like and 11 luminal cancers matched for tumour grade. RESULTS: High Treg infiltration correlated with tumour CXCL12 positivity (OR 1.89, 95% CI 1.22 to 2.94, P = 0.004) and basal phenotype (OR 3.14, 95% CI 1.08 to 9.17, P = 0.004) in univariate and multivariate analyses. CXCL12 positivity correlated with improved survival (P = 0.005), whereas high Treg correlated with shorter survival for all breast cancers (P = 0.001), luminal cancers (P < 0.001) and basal-like cancers (P = 0.040) that were confirmed in a multivariate analysis (OR 1.61, 95% CI 1.02 to 2.53, P = 0.042). In patients treated with hormone therapy, high Treg were associated with a shorter survival in a multivariate analysis (OR 1.78, 95% CI 1.01 to 3.15, P = 0.040). There was a tendency for luminal cancers to show CXCL12 expression (102/138, 74%) compared to basal-like cancers (16/27, 59%), which verged on statistical significance (P = 0.050). Up-regulation of CXCR4 in Treg correlated with the basal-like phenotype (P = 0.029) and tumour hypoxia, as indicated by CA9 expression (P = 0.049). CONCLUSIONS: Our data show that in the setting of hypoxia and CXCR4 up-regulation in Treg, CXCL12 expression may have the negative consequence of enhancing Treg recruitment and suppressing the anti-tumour immune response. More... »

PAGES

r47

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/bcr2869

    DOI

    http://dx.doi.org/10.1186/bcr2869

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013798262

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21521526


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