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

转录因子叉头盒蛋白3（FOXP3）不仅在调节性T细胞（Tregs）中高表达，在肿瘤细胞中也高表达。FOXP3通过treg及其对肿瘤耐受性的影响具有肿瘤增强作用，但也作为几种癌基因的有效抑制因子抑制肿瘤发生。本研究采用免疫组织化学方法研究FOXP3在乳腺癌患者肿瘤细胞及淋巴细胞浸润中的表达与预后的关系。100例原发性浸润性乳腺癌（包括23例her2过表达标本）中，63%的肿瘤细胞为foxxp +， 57%的肿瘤细胞为FOXP3+淋巴细胞高浸润。FOXP3在肿瘤细胞中的表达无预后意义，而FOXP3+淋巴细胞与较差的总生存期显著相关（OS; n=98， log-rank检验p=0.008）。在肿瘤细胞中观察到FOXP3的异质性亚细胞定位（细胞质，31%；细胞核，26%；两者，6%），有趣的是，细胞质和细胞核FOXP3分别与不良（p=0.058）和改善（p=0.016） OS相关。这些发现提示FOXP3在淋巴细胞和肿瘤细胞中的表达可能是乳腺癌的预后标志物。FOXP3在肿瘤细胞中的定位可能具有不同的生物学活性和预后价值，有助于确定合适的治疗方案。

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.