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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 localization 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-tumoral or stromal groups, based on whether they had higher or lower than median densities of specific tumor-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 tumors 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" tumors were also characterized 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" tumor microenvironment, in contrast to tumors 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 favorable prognostic panel in TNBCs. These data also indicate new avenues for further investigation on the interaction between immune cell types within the tumor microenvironment and highlight the potential of Treg density and localization within tumors to affect clinical outcome.