Guan Honggeng, Wan Yuqiu, Lan Jing, Wang Qin, Wang Zhangyu, Li Yecheng, Zheng Jiqing, Zhang Xueguang, Wang Zemin, Shen Yueping, Xie Fang
The Department of Pathology, Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, P. R. China.
Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, P. R. China.
Sci Rep. 2016 Oct 20;6:35651. doi: 10.1038/srep35651.
Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19 CD24 CD38 regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4 CD25 CD127 Tregs (r = 0.316, P = 0.001). We found that PD-L1 expression was higher on Bregs in IBCa patients compared with patients with FIBma or healthy individuals (P < 0.05, respectively), and that a tight correlation exists between CD19 CD24 CD38 PD-L1 Bregs and CD19 CD24 CD38 Bregs (r = 0.267, P = 0.007), poor TNM phases and up-regulated expression of PD-L1 on Bregs. The pattern of PD-1 expression on CD4 T cells indicated that high level of PD-1 expressed on CD4 CD25 CD127 effector T cells (P < 0.001). More importantly, the presence of PD-L1 on Bregs was positively correlated with Tregs (r = 0.299, P = 0.003), but negatively correlated with PD-1 effector T cells (r = -0.22, P = 0.031). Together, results of the present study indicated that PD-L1 is an important molecule on Bregs, mediated the generation of Tregs in IBCa.
调节性T细胞（Tregs）是调节抗肿瘤免疫抑制、肿瘤免疫逃逸、转移和复发的关键介质，被认为是人类癌症免疫治疗的重要靶点。在本研究中，与纤维腺瘤（FIBma）患者或健康个体相比，浸润性乳腺癌（IBCa）患者外周血单个核细胞（PBMCs）中CD19 CD24 CD38调节性B细胞（Bregs）升高，且Bregs与CD4 CD25 CD127 Tregs之间存在正相关（r = 0.316，P = 0.001）。我们发现，与FIBma患者或健康个体相比，IBCa患者Bregs上的PD-L1表达更高（P分别< 0.05），且CD19 CD24 CD38 PD-L1 Bregs与CD19 CD24 CD38 Bregs之间存在紧密相关性（r = 0.267，P = 0.007），TNM分期较差且Bregs上PD-L1表达上调。CD4 T细胞上PD-1的表达模式表明，CD4 CD25 CD127效应T细胞上表达高水平的PD-1（P < 0.001）。更重要的是Bregs上PD-L1的存在与Tregs呈正相关（r = 0.299，P = 0.003），但与PD-1效应T细胞呈负相关（r = -0.22，P = 0.031）。总之，本研究结果表明PD-L1是Bregs上的重要分子，介导了IBCa中Tregs的产生。
