In breast cancer, a high ratio of tumour-infiltrating intraepithelial CD8+ to FoxP3+ cells is characteristic for the medullary subtype.

AIMS: Medullary breast cancer (MBC) is a biologically distinct subtype of breast cancer characterized by prominent lymphocytic infiltrates and a favourable clinical outcome. Tumour-infiltrating CD8+ effector T cells may contribute to the good prognosis of this type of cancer; however, certain subtypes of lymphocyte, such as FoxP3+ regulatory T cells (Tregs), can also suppress antitumour immunity.

METHODS AND RESULTS: We determined tumour infiltration by FoxP3+, CCL22+ and CD8+ cells in paraffin-embedded sections of MBC, and, as a reference, in samples of grade 3 ductal, lobular and mucinous breast cancer. All analysed MBCs were strongly infiltrated by FoxP3+ cells, whereas only weak infiltrates were detected in ductal or lobular breast cancer. This finding was unexpected, given the good prognosis of MBC. Strikingly, the number of CD8+ T cells exceeded the number of FoxP3+ cells in MBC (ratio of CD8+ to FoxP3+ cells of 2.6), whereas equal amounts of both cell types were found in ductal breast cancer (ratio of CD8+ to FoxP3+ cells of 1.1). In both types of breast cancer, we also detected cells expressing the Treg-attracting chemokine CCL22.

CONCLUSIONS: In breast cancer, a predominance of tumour-infiltrating CD8+ over FoxP3+ cells was observed in MBC. Thus, the ratio of CD8+ to FoxP3+ cells rather than the absolute number of intratumoral FoxP3+ cells may be predictive for the clinical outcome of cancer.