%0 Journal Article
%T Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers
%A Max Yan
%A Nicholas Jene
%A David Byrne
%A Ewan KA Millar
%A Sandra A O'Toole
%A Catriona M McNeil
%A Gaynor J Bates
%A Adrian L Harris
%A Alison H Banham
%A Robert L Sutherland
%A Stephen B Fox
%J Breast Cancer Research
%D 2011
%I BioMed Central
%R 10.1186/bcr2869
%X 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.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).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.Cancer is rarely suppressed by the host immune response since tumour cells acquire immune tolerance. The failure of an anti-cancer immune response may be due to a specific subpopulation of regulatory T cells (Treg) [1]. Treg down-regulate the activation and expansion of self-reactive lymphocytes [2], and are crucial for the repression of autoimmune disorders and transplant rejection [3,4]. Although the role of Treg in cancer has not been fully elucidated,
%U http://breast-cancer-research.com/content/13/2/R47