A novel MDSC-induced PD-1-PD-L1+ B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties
A novel MDSC-induced PD-1-PD-L1+ B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties
复制标题
乳腺肿瘤微环境中新型 MDSC 诱导的 PD-1(-)PD-L1( ) B 细胞亚群具有免疫抑制特性
DOI：
10.1080/2162402x.2017.1413520
复制
发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Ren, Xiubao
中科院分区：
文献类型：
--
作者：
Shen, Meng;Wang, Jian;Ren, Xiubao
髓源性抑制细胞（MDSC）是一组异质性骨髓细胞，可抑制肿瘤微环境中的T细胞活性。然而，MDSC对B细胞的抑制作用及其机制尚不清楚。在这里，我们表明，在4 T1乳腺癌小鼠中，与正常小鼠相比，与脾B细胞平行的MDSC数量显著增加。在MDSC存在下，B细胞的表面分子被重塑，PD-1和PD-L1等检查点相关分子发生显著变化。MDSC还作为B细胞免疫功能（如增殖、凋亡和分泌抗体和细胞因子的能力）的重要调节剂出现。我们的研究进一步证实了MDSC可以将正常的B细胞转化为免疫调节B细胞（B细胞）的亚型，其抑制T细胞应答。此外，我们还鉴定了一种新的具有特异性表型PD-1（-）PD-L1（+）CD 19（+）的BclB细胞，与先前报道的以CD 1d（+）CD 5（+）CD 19（+）、CD 5（+）CD 19（+）和白细胞介素（IL）-10分泌型B细胞为特征的BclB细胞相比，其对T细胞的抑制作用最大。我们的研究结果强调了MDSC调节B细胞反应，并可作为抗肿瘤治疗的治疗方法。对这种新的布雷格亚型的研究扩展了我们对T细胞应答调节的理解，并为抗肿瘤免疫和免疫治疗提供了新的思路。
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells that suppress T-cell activity in a tumor microenvironment. However, the suppressive function of MDSCs on B cells and its underlying mechanism remain unclear. Here, we show that in 4T1 breast cancer mice, a significantly increased number of MDSCs, in parallel with splenic B cells, are accumulated when compared to normal mice. In the presence of MDSCs, the surface molecules of B cells are remolded, with checkpoint-related molecules such as PD-1 and PD-L1 changing prominently. MDSCs also emerge as vital regulators in B-cell immune functions such as proliferation, apoptosis and the abilities to secrete antibodies and cytokines. Our study further identifies that MDSCs can transform normal B cells to a subtype of immuno-regulatory B cells (Bregs) which inhibit T-cell response. Furthermore, we identified a novel kind of Bregs with a specific phenotype PD-1(-)PD-L1(+)CD19(+), which exert the greatest suppressive effects on T cells in comparison with the previously reported Bregs characterized as CD1d(+)CD5(+)CD19(+), CD5(+)CD19(+) and Interleukin (IL)-10-secreting B cells. Our results highlight that MDSCs regulate B-cell response and may serve as a therapeutic approach in anti-tumor treatment. Investigation of this new Breg subtype extends our understanding of regulation of T-cell response and sheds new light on anti-tumor immunity and immune therapy.