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http://crossmark.crossref.org/dialog/?doi=10.1007/s10549-017-4161-4&domain=pdf
Web End = Breast Cancer Res Treat (2017) 163:2135 DOI 10.1007/s10549-017-4161-4
http://crossmark.crossref.org/dialog/?doi=10.1007/s10549-017-4161-4&domain=pdf
Web End = PRECLINICAL STUDY
Higher densities of Foxp3+ regulatory T cells are associated with better prognosis in triple-negative breast cancer
Joe Yeong1,2 Aye Aye Thike1 Jeffrey Chun Tatt Lim1 Bernett Lee2
Huihua Li3 Siew-Cheng Wong2 Susan Swee Shan Hue1 Puay Hoon Tan1
Jabed Iqbal1
Received: 25 October 2016 / Accepted: 13 February 2017 / Published online: 23 February 2017 Springer Science+Business Media New York 2017
AbstractPurpose 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 clinico-pathological 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 specic tumour-inltrating lymphocyte populations (CD3? total T cells, Foxp3?CD3? Tregs, or CD20? B cells) in the intratumoural space or stroma.
Results Of the 164 samples, patients bearing tumours with high Tregs within their intra-tumoural, but not stromal, areas experienced signicantly longer overall and disease-free survival compared to individuals with low Treg densities. These high intra-tumoural Treg tumours were also char-acterised by relatively higher frequencies of CD8? T cells
and CD20? B cells, and expressed signicantly higher levels of some genes associated with inammation, immune cell functions and trafcking, 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.
Keywords Triple-negative breast cancer Regulatory T
cells Foxp3 Tumour-inltrating lymphocytes Immune
cells Survival Immunohistochemistry
Immunouorescence Gene expression
Introduction
Triple-negative breast cancers (TNBCs), dened by the absence of oestrogen receptor (ER), progesterone receptor (PR) and c-erbB2 (HER2), account for between 9 and 17%...