Yeong Joe, Thike Aye Aye, Lim Jeffrey Chun Tatt, Lee Bernett, Li Huihua, Wong Siew-Cheng, Hue Susan Swee Shan, Tan Puay Hoon, Iqbal Jabed
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.
Breast Cancer Res Treat. 2017 May;163(1):21-35. doi: 10.1007/s10549-017-4161-4. Epub 2017 Feb 23.
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.
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, Foxp3CD3 Tregs, or CD20 B cells) in the intra-tumoural space or stroma.
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.
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.
表达叉头框蛋白3（Foxp3）的调节性T细胞（Tregs）在乳腺癌中的作用仍不明确。我们检测了三阴性乳腺癌（TNBC）样本中总T细胞、B细胞和Tregs的丰度及定位，并探讨这些参数是否与癌症的临床病理特征或临床结局相关。
将2003年至2010年在新加坡诊断的TNBC样本，根据肿瘤内或基质中特定肿瘤浸润淋巴细胞群体（CD3总T细胞、Foxp3⁺CD3⁺ Tregs或CD20 B细胞）的密度高于或低于中位数，分为“高”和“低”肿瘤内或基质组。
在164个样本中，肿瘤内（而非基质）区域Tregs高的患者与Treg密度低的个体相比，总生存期和无病生存期显著更长。这些“肿瘤内Treg高”的肿瘤还具有相对较高频率的CD8⁺ T细胞和CD20⁺ B细胞，并表达一些与炎症、免疫细胞功能和迁移相关的基因水平显著更高，这与Tregs密度较低的肿瘤相比，完全符合更“免疫激活”的肿瘤微环境。
总之，肿瘤内Tregs、CD8⁺ T细胞和CD20⁺ B细胞的高密度组合代表了TNBC中一个有利的预后指标。这些数据还为进一步研究肿瘤微环境中免疫细胞类型之间的相互作用指明了新途径，并突出了肿瘤内Treg密度和定位影响临床结局的潜力。
