title: Higher densities of Foxp3+regulatory T cells are associated with better prognosis in triple-negative breast cancer.
abstract: OBJECTIVE
  The role of Forkhead Box Protein 3 (Foxp3) expressing regulatory T cells (Tregs) in breast cancer remains unclear. We examined the abundance and localisation of total T cells, B cells and Tregs within samples from triple-negative breast cancers (TNBCs) and asked whether these parameters were associated with clinicopathological features of the cancer or clinical outcomes.
  
  
  METHODS
  Samples from TNBCs diagnosed between 2003 and 2010 in Singapore were divided into "high" and "low" intra-tumoural or stromal groups, based on whether they had higher or lower than median densities of specific tumour-infiltrating lymphocyte populations (CD3+total T cells, Foxp3+CD3+Tregs, or CD20+B cells) in the intra-tumoural space or stroma.
  
  
  RESULTS
  Of the 164 samples, patients bearing tumours with high Tregs within their intra-tumoural, but not stromal, areas experienced significantly longer overall and disease-free survival compared to individuals with low Treg densities. These "high intra-tumoural Treg" tumours were also characterised by relatively higher frequencies of CD8+T cells and CD20+B cells, and expressed significantly higher levels of some genes associated with inflammation, immune cell functions and trafficking, altogether consistent with a more "immune-activated" tumour microenvironment, in contrast to tumours bearing lower densities of Tregs.
  
  
  CONCLUSIONS
  In summary, the combination of high densities of intra-tumoural Tregs, CD8+T cells and CD20+B cells represents a favourable prognostic panel in TNBCs. These data also indicate new avenues for further investigation on the interaction between immune cell types within the tumour microenvironment and highlight the potential of Treg density and localisation within tumours to affect clinical outcome.
authors.affiliation: Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.|Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Joe
authors.initials: J
authors.lastname: Yeong
authors.affiliation: Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.affiliation: Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
authors.forename: Jeffrey Chun Tatt
authors.initials: JC
authors.lastname: Lim
authors.affiliation: Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Division of Medicine, Singapore General Hospital, Singapore, Singapore.
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.affiliation: Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Siew-Cheng
authors.initials: SC
authors.lastname: Wong
authors.affiliation: Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
authors.forename: Susan Swee Shan
authors.initials: SS
authors.lastname: Hue
authors.affiliation: Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
authors.affiliation: Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore. jabed.iqbal@singhealth.com.sg.
authors.forename: Jabed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000276:immunology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Foxp3; Gene expression; Immune cells; Immunofluorescence; Immunohistochemistry; Regulatory T cells; Survival; Triple-negative breast cancer; Tumour-infiltrating lymphocytes