Immunological study of HER2+breast cancer-study of strategy for effective cancer-immunotherapy

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The transcription factor forkhead box protein3(FOXP3) is highly expressed not only in regulatory T cells(Tregs), but also in tumor cells. FOXP3 possesses a tumor-enhancing role through Tregs and their effect on tumor tolerance, but also suppresses carcinogenesis as a potent repressor of several oncogenes. In this study, we immunohistochemically studied the prognostic significance of FOXP3 expression both in tumor cells and tumor infiltrates of lymphocytes in breast cancer patients.Of 100 tumor specimens with primary invasive breast carcinoma(including 23 HER2-overexpressing specimens), 63% and 57% were evaluated as FOXP+tumor cells and high infiltrate of FOXP3+lymphocytes, respectively. FOXP3 expression in tumor cells did not show prognostic significance, while FOXP3+lymphocytes was significantly associated with poor overall survival(OS ; n=98, log-rank test p=0.008). The heterogeneous subcellular localization of FOXP3 was observed in tumor cells(cytoplasm, 31%; nucleus, 26%; and both, 6%), and interestingly, cytoplasmic and nuclear FOXP3 were associated with poor(p=0.058) and improved(p=0.016) OS, respectively. These findings indicate that FOXP3 expression in both lymphocytes and tumor cells could be a prognostic marker for breast cancer. FOXP3 in tumor cells might have distinct biological activities and prognostic values according to the localization, which would be help identify appropriate therapy for the patients.