Liu Shuzhen, Foulkes William D, Leung Samuel, Gao Dongxia, Lau Sherman, Kos Zuzana, Nielsen Torsten O
Breast Cancer Res. 2014 Sep 6;16(5):432. doi: 10.1186/s13058-014-0432-8.
The infiltration of FOXP3+ regulatory T cells into invasive tumors has been reported to be associated with survival in a variety of cancers. The prognostic significance of FOXP3+ tumor-infiltrating lymphocytes (TILs) in breast cancer, however, remains controversial.
FOXP3+ TILs were assessed by immunohistochemistry on tissue microarrays constructed from a well-defined cohort of 3,992 breast cancer patients linked to detailed demographic, biomarker, treatment and outcome data. Survival analyses were performed using the Kaplan-Meier function and Cox proportional hazards regression models to evaluate the association of FOXP3+ TILs with breast cancer-specific survival, stratified by intrinsic subtype and cytotoxic T-cell infiltration status (as defined by CD8 immunohistochemistry).
The presence of high numbers of FOXP3+ TILs was significantly associated with young age, high grade, estrogen receptor (ER) negativity, concurrent CD8+ cytotoxic T-cell infiltration, and human epidermal growth factor receptor-2 positive (HER2+)/ER- and core basal subtypes. On multivariate survival analysis, a high level of FOXP3+ TILs was significantly associated with poor survival in ER+ breast cancers that lacked CD8+ T-cell infiltrates (hazard ratio (HR) = 1.30, 95% confidence interval (CI) = 1.02 to 1.66). However, in ER- breast cancers, FOXP3+ TILs were strongly associated with improved survival in the HER2+/ER- subgroup, particularly in those with co-existent CD8+ T-cell infiltrates (HR = 0.48, 95% CI = 0.23 to 0.98), for which the presence of high levels of FOXP3+ TILs was independent of standard clinical prognostic factors.
FOXP3+ regulatory TILs are a poor prognostic indicator in ER+ breast cancer, but a favorable prognostic factor in the HER2+/ER- subtype. The prognostic value of FOXP3+ TILs in breast cancer differs depending on ER and HER2 expression status and CD8+ T-cell infiltration.
据报道，FOXP3 +调节性T细胞浸润侵袭性肿瘤与多种癌症的生存率相关。然而，FOXP3 +肿瘤浸润淋巴细胞（TILs）在乳腺癌中的预后意义仍存在争议。
通过免疫组织化学对由3992例乳腺癌患者组成的明确队列构建的组织微阵列进行FOXP3 + TILs评估，这些患者关联了详细的人口统计学、生物标志物、治疗和结局数据。使用Kaplan-Meier函数和Cox比例风险回归模型进行生存分析，以评估FOXP3 + TILs与乳腺癌特异性生存的关联，并按内在亚型和细胞毒性T细胞浸润状态（由CD8免疫组织化学定义）分层。
大量FOXP3 + TILs的存在与年轻、高级别、雌激素受体（ER）阴性、同时存在CD8 +细胞毒性T细胞浸润以及人表皮生长因子受体2阳性（HER2 +）/ ER -和核心基底亚型显著相关。在多因素生存分析中，高水平的FOXP3 + TILs与缺乏CD8 + T细胞浸润的ER +乳腺癌患者的不良生存显著相关（风险比（HR）= 1.30，95%置信区间（CI）= 1.02至1.66）。然而，在ER -乳腺癌中，FOXP3 + TILs与HER2 + / ER -亚组的生存改善密切相关，特别是在那些同时存在CD8 + T细胞浸润的患者中（HR = 0.48，95% CI = 0.23至0.98），高水平的FOXP3 + TILs的存在独立于标准临床预后因素。
FOXP3 +调节性TILs在ER +乳腺癌中是不良预后指标，但在HER2 + / ER -亚型中是有利的预后因素。FOXP3 + TILs在乳腺癌中的预后价值因ER和HER2表达状态以及CD8 + T细胞浸润而异。
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