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Higher densities of Foxp3+ regulatory T cells are associated with better prognosis in triple-negative breast cancer

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

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.

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Funding

This study was funded by the SingHealth Duke-NUS Pathology Academic Clinical Program Budding Clinician-Scientist grant (ACP PATH BCS 14 001), A*STAR Biomedical Research Council, National Medical Research Council Stratified Medicine Programme Office (SMPO201302) awarded to Dr. Puay Hoon Tan and a Transition Award from the Singapore National Medical Research Council (NMRC/TA/0041/2015) awarded to Dr. Jabed Iqbal.

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Authors and Affiliations

  1. Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore

    Joe Yeong, Aye Aye Thike, Jeffrey Chun Tatt Lim, Susan Swee Shan Hue, Puay Hoon Tan & Jabed Iqbal

  2. Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore

    Joe Yeong, Bernett Lee & Siew-Cheng Wong

  3. Division of Medicine, Singapore General Hospital, Singapore, Singapore

    Huihua Li

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Yeong, J., Thike, A.A., Lim, J.C.T. et al. Higher densities of Foxp3+ regulatory T cells are associated with better prognosis in triple-negative breast cancer. Breast Cancer Res Treat 163, 21–35 (2017). https://doi.org/10.1007/s10549-017-4161-4

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