Journal
BRITISH JOURNAL OF CANCER
Volume 108, Issue 1, Pages 155-162Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.524
Keywords
FOXP3; Treg; tumour immunity breast cancer; oestrogen receptor; prognosis
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Funding
- BC Cancer Agency Tumour Tissue Repository
- Manitoba Breast Tumour Bank
- Canadian Institutes of Health Research (CIHR) [MOP-64349]
- Canadian Breast Cancer Foundation
- BC Cancer Foundation
- US DOD breast cancer research program [W81XWH-08-1-0781]
- Natural Sciences and Engineering Research Council of Canada
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Background: Regulatory T cells (Tregs) are commonly identified by expression of the transcription factor FOXP3 and are conventionally thought to promote cancer progression by suppressing anti-tumour immune responses. We examined the relationship between FOXP3(+) tumour-infiltrating lymphocytes (TIL) and prognosis in oestrogen receptor (ER)-negative breast cancer, a tumour subtype with poor clinical outcome in which TIL are abundant. Methods: FOXP3(+) and CD8(+) TIL were assessed by immunohistochemistry in a cohort of 175 ER-breast tumours. Results were confirmed in an independent data set of 78 ER-breast tumours with publically available gene expression data. Results: High FOXP3(+) TIL levels were strongly associated with prolonged recurrence-free survival (HR = 0.461, P = 0.0002), particularly among basal-like tumours (HR = 0.280, P = 0.0001), for which FOXP3 status was independent of standard prognostic factors. Over 75% of FOXP3(+) TIL in triple negative breast tumours displayed a conventional CD4(+)CD25(+) Treg phenotype. Importantly, FOXP3(+) TIL were positively correlated with CD8(+) (cytotoxic) T cells (r(s) = 0.76, P<0.0001), and were prognostically insignificant in tumours with low levels of CD8(+) TIL. These observations were confirmed in an independent cohort. Conclusion: In contrast with current dogma, we show for the first time that FOXP3(+) TIL are associated with robust anti-tumour immunity and favourable prognosis in ER-breast cancer.
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