The Peritumoral CD8+/FOXP3+ Cell Ratio Has Prognostic Value in Triple-negative Breast Cancer

Compelling data has demonstrated the prognostic significance of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), a subtype generally associated with a poor clinical outcome but highly heterogeneous in nature. There have been limited studies investigating the importance of subsets of T cells in TILs. Further, the significance of intratumoral versus peritumoral TILs remains controversial. We examined the prognostic value of tumor-associated CD8 + cytotoxic T cells and FOXP3 + regulatory T cells in 35 chemotherapy-naive TNBC cases with a tumor-host interface in the tissue sections. The CD8 + and FOXP3 + cell count was expressed by immunoreactive cells per high-power field in an average of 10 high-power fields. There was a wide range of CD8 + and FOXP3 + T cells within the peritumoral and intratumoral stroma. Both CD8 + and FOXP3 + TILs were significantly higher at the former location as compared with the latter ( P <0.0001 and 0.003, respectively). The numbers of CD8 + and FOXP3 + T cells, either within peritumoral or intratumoral stroma, were not significantly associated with distant relapse-free or disease-specific survival. However, the peritumoral CD8 + /FOXP3 + ratio of TILs was significantly associated with prolonged relapse-free survival ( P =0.04) and disease-specific survival ( P =0.02). This association was not observed with the CD8 + /FOXP3 + ratio of intratumoral TILs. These observations suggest that the immunologic balance in the tumor microenvironment might determine antitumor immunity. Further, the peritumoral TILs appear to play a more important role in the progression of TNBC when compared with the intratumoral TILs, thus reaffirming the necessity of revisiting the method for the assessment of TILs.