Tumour-infiltrating FOXP3+ lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer

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 (rs=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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