CD19(+)IL-10(+) regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4(+) T cells to CD4(+)Foxp3(+) regulatory T cells
CD19(+)IL-10(+) regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4(+) T cells to CD4(+)Foxp3(+) regulatory T cells
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CD19( )IL-10( ) 调节性 B 细胞影响舌鳞状细胞癌患者的生存并诱导静息 CD4( ) T 细胞转变为 CD4( )Foxp3( ) 调节性 T 细胞
DOI：
10.1016/j.oraloncology.2015.11.003
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发表时间：
2016
期刊：
影响因子：
4.8
通讯作者：
Liao Gui-Qing
中科院分区：
文献类型：
--
作者：
Zhou Xi;Su Yu-Xiong;Lao Xiao-Mei;Liang Yu-Jie;Liao Gui-Qing
目的调节性T细胞(Tregs)在肿瘤微环境中的增加预示着包括舌鳞状细胞癌(TSCC)在内的各种癌症患者的预后较差。最近，Tregs和调节性B细胞(Bregs)之间的串扰已经在几个肿瘤模型中被显示出来。然而，Bregs与人类肿瘤免疫的相关性仍然难以捉摸。本研究的目的是探讨Bregs在TSCC微环境中的分布和功能。材料和方法对46例TSCC、20个转移淋巴结和癌旁正常组织进行Bregs：IL10/CD19和Tregs：Foxp3/CD4双重染色。结果免疫组织化学(IHC)结果显示，舌鳞癌组织中Bregs/CD19+B的比例(0.80±0.08%)显著高于癌旁正常组织(0.52±0.04%p<；P<；0.01)；−T细胞的Bregs/CD19+B比例(0.80±0.08%)明显高于癌旁正常组织(0.52±0.04%p<；0.01)。TSCC微环境中Bregs的增加与Tregs有关，并预示患者的预后较差。细胞学实验表明，与舌鳞癌细胞共培养后，Bregs的表达频率增加，诱导的B细胞可将−+CD25T细胞转化为Treg细胞。结论舌鳞癌微环境中Bregs的高表达对静止的CD4+T细胞的分化起重要作用，并影响患者的预后。
ObjectivesIncrease of regulatory T cells (Tregs) in the tumor microenvironment predicts worse survival of patients with various types of cancer including tongue squamous cell carcinoma (TSCC). Recently, the cross-talk between Tregs and regulatory B cells (Bregs) has been shown in several tumor models. However the relevance of Bregs to tumor immunity in humans remains elusive. Our objective was to investigate the distribution and function of Bregs in TSCC microenvironment.Materials and MethodsDouble staining (Bregs: IL10/CD19 and Tregs: Foxp3/CD4) was performed on tissue sections of 46 TSCC, 20 metastasis lymph nodes, and tumor adjacent normal tissue. Flow cytometry analysis was used to detect the Bregs from magnetic bead-sorted B cells after co-culture with TSCC cell lines, and Tregs from sorted CD4+CD25−T cells after co-culture with stimulated B cells.ResultsThe immunohistochemical (IHC) results showed that the frequency of Bregs/CD19+B in TSCC (0.80 ± 0.08%) was significantly higher than adjacent normal tissue (0.52 ± 0.04%p< 0.01). And the increase of Bregs in TSCC microenvironment was related to Tregs and predicts worse survival in patients. Cytological experiments indicated that frequency of Bregs increased after co-culture with TSCC cell line and that the induced B cells converted CD4+CD25−T cells into Tregs.ConclusionThe increased expression of Bregs in the TSCC microenvironment plays a significant role in the differentiation of resting CD4+T cells and influenced the prognosis of TSCC patients.