Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4⁺ T cells to T-regulatory cells.
Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4⁺ T cells to T-regulatory cells.
复制标题
DOI：
10.1158/0008-5472.can-10-4316
复制
发表时间：
2011-05-15
期刊：
影响因子：
11.2
通讯作者：
Biragyn A
中科院分区：
文献类型：
--
作者：
Olkhanud PB;Damdinsuren B;Bodogai M;Gress RE;Sen R;Wejksza K;Malchinkhuu E;Wersto RP;Biragyn A
乳腺癌的肺转移需要募集和扩增T调节细胞（TCFs），其促进逃避宿主保护性免疫细胞。然而，目前尚不清楚肿瘤如何招募TGFAP来支持转移性生长。在这里，我们报告了一个独特的和以前未描述的调节B细胞亚群的机制参与。这些细胞被称为肿瘤诱发的B2细胞（tB 2），表型类似于活化但增殖性差的成熟B2细胞（CD 19 + CD 25 High CD 69 High），表达组成型活性Stat 3和B7-H1 High CD 81 High CD 86 High CD 62 LLowIgMInt。我们对小鼠4 T1乳腺癌模型的研究表明，tBcR在肺转移中的主要作用是诱导FoxP 3 + TcR从静息CD 4 + T细胞的TGFβ依赖性转化。在没有tBl的情况下，由于Treg转化较差，4 T1肿瘤不能有效转移到肺中。我们的研究结果具有重要的临床意义，因为它们表明必须控制tBl，以中断对支持癌症转移至关重要的关键癌症诱导的免疫抑制事件的启动。
Pulmonary metastasis of breast cancer requires recruitment and expansion of T regulatory cells (Tregs) that promote escape from host protective immune cells. However, it remains unclear precisely how tumors recruit Tregs to support metastatic growth. Here we report the mechanistic involvement of a unique and previously undescribed subset of regulatory B cells. These cells, designated tumor-evoked Bregs (tBregs), phenotypically resemble activated but poorly proliferative mature B2 cells (CD19+ CD25High CD69High) that express constitutively active Stat3 and B7-H1High CD81High CD86High CD62LLowIgMInt. Our studies with the mouse 4T1 model of breast cancer indicate that the primary role of tBregs in lung metastases is to induce TGFβ-dependent conversion of FoxP3+ Tregs from resting CD4+ T cells. In the absence of tBregs, 4T1 tumors cannot metastasize into the lungs efficiently due to poor Treg conversion. Our findings have important clinical implications, since they suggest that tBregs must be controlled to interrupt the initiation of a key cancer-induced immunosuppressive event that is critical to support cancer metastasis.