title: Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, 2410 Lee Avenue, Victoria, BC V8R 6V5, Canada.
authors.forename: N R
authors.initials: NR
authors.lastname: West
authors.forename: S E
authors.initials: SE
authors.lastname: Kost
authors.forename: S D
authors.initials: SD
authors.lastname: Martin
authors.forename: K
authors.initials: K
authors.lastname: Milne
authors.forename: R J
authors.initials: RJ
authors.lastname: Deleeuw
authors.forename: B H
authors.initials: BH
authors.lastname: Nelson
authors.forename: P H
authors.initials: PH
authors.lastname: Watson
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D046888:Tissue Array Analysis
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors