PD-L1 Expression Is Associated with Tumor FOXP3(+) Regulatory T-Cell Infiltration of Breast Cancer and Poor Prognosis of Patient.
PD-L1 Expression Is Associated with Tumor FOXP3(+) Regulatory T-Cell Infiltration of Breast Cancer and Poor Prognosis of Patient.
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PD-L1 表达与乳腺癌肿瘤 FOXP3 调节性 T 细胞浸润及患者不良预后相关
DOI：
10.7150/jca.14549
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发表时间：
2016
影响因子：
3.9
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Li Z;Dong P;Ren M;Song Y;Qian X;Yang Y;Li S;Zhang X;Liu F
背景：PD-L1的表达已被估计用于预测实体瘤中PD-L1抑制的治疗潜力。最近的研究表明，PD-L1在调节性T细胞（Treg）发育和功能维持中起着关键作用。虽然FOXP 3 +Treg浸润和PD-L1表达的增加已在几种恶性肿瘤中发现，但它们在人类乳腺肿瘤中的相关性尚不清楚。方法：采用免疫组织化学方法检测501例乳腺癌组织中PD-L1和FOXP 3的表达。研究其表达与临床病理特征、肿瘤内在亚型及患者预后的关系。结果如下：在该乳腺癌患者队列中，肿瘤组织中的PD-L1表达和FOXP 3 +Treg浸润表现出高度相关性（rs=0.334，p<0.001）。PD-L1高表达和FOXP 3 +Treg浸润增加均与高组织学分级、阴性ER和PR状态以及侵袭性内在肿瘤亚型（尤其是基底细胞样亚型）相关。两种标记物同时高表达的肿瘤预后最差。多变量分析证明，这两种标志物是患者总生存期降低的独立预测因子，特别是在基底细胞样亚型中。结论：结果表明，PD-L1和FOXP 3 + TcR可能协同作用，其上调表达促进乳腺癌的肿瘤免疫逃避。旨在阻断PD-L1和消耗Tcl 3的组合免疫治疗方法可能会提高乳腺癌患者的治疗效果，特别是那些患有基底样癌的患者。
Background: Expression of PD-L1 has been estimated to predict the therapeutic potential of PD-L1 inhibition in solid tumors. Recent studies have demonstrated that PD-L1 plays a critical role in regulatory T-cell (Treg) development and functional maintenance. Although increases in FOXP3+Treg infiltration and PD-L1 expression have been revealed in several malignancies, their correlation in human breast tumors is as yet unclear. Methods: Whole-tissue sections from 501 patients with breast cancer were examined for PD-L1 and FOXP3 expression by immunohistochemistry. Correlation between their expressions and the association with clinicopathological features, intrinsic tumor subtypes and patient's prognosis were studied. Results: PD-L1 expression and FOXP3+Treg infiltrates in tumor tissue demonstrated a high correlation (rs=0.334, p<0.001) in this cohort of breast cancer patients. High PD-L1 expression and increased FOXP3+Treg infiltrates were both associated with high histological grade, negative ER and PR status, and aggressive intrinsic tumor subtypes, especially the basal-like subtype. Tumors with concomitant high expressions of the two markers had the worst prognosis. Multivariate analysis proved both markers to be the independent predictors for decreased overall survival of patients, particularly in the basal-like subtype. Conclusions: The results suggest that PD-L1 and FOXP3+Tregs may work synergistically and their up-regulated expressions promote tumor immune evasion in breast cancer. Combinatorial immunotherapeutic approaches aiming on blocking PD-L1 and depleting Tregs might improve therapeutic efficacy in breast cancer patients, especially those with basal-like carcinoma.