MDSCs是一类与肿瘤免疫逃逸密切相关的髓系细胞，以往的研究主要集中于它们对T细胞及NK细胞等细胞的免疫调控作用，关于MDSCs对B细胞的免疫调控尚未阐明。前期结果表明乳腺癌MDSCs激活 PD-1-PD-L1+B细胞CyclinD-CDK4/6-pRb轴，并证实该B细胞具有免疫抑制功能。阻断CDK能够逆转B细胞表面PD-L1的表达并减弱B细胞的免疫抑制功能。进一步发现阻断TGF-β能够抑制B细胞下游Smad2/3磷酸化及Smad4入核，并抑制B细胞中CDK通路的激活。本课题将以BALB/C小鼠4T1乳腺癌为模型，阐明乳腺癌MDSCs通过TGF-β-Smad途径调控CDK通路，继而影响PD-1-PD-L1+B细胞的免疫抑制功能。本项目的完成将有助于了解B细胞的免疫抑制作用，同时为抗肿瘤免疫效应机制以及肿瘤治疗新方法的研究提供一定的理论基础。

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 successfully constructed BALB/C mice 4T1 breast cancer model. We show that the surface molecules of B cells are remolded, with checkpoint-related molecules such as PD-1 and PD-L1 changing prominently in the presence of MDSCs. The subset of PD-1-PD-L1+B cells was obviously increased in the presence of MDSCs. MDSCs emerge as vital regulators in B-cell inhibitory immune functions such as proliferation inhibition on normal T cells and transformation of Th1 to Th2. Further detection by flow cytometry showed that TGF-β in breast cancer MDSCs increased. Analysis by western blot demonstrated that molecules of CyclinD1, CyclinD3, CDK4/6, pRb in PD-1-PD-L1+B cells increased. Application of inhibitors targeting TGF-β or CDK4/6 could reverse PD-L1 expression on B cells and further attenuate PD-1-PD-L1+B cells′ suppression on proliferation of normal T cells. Blockage of TGF-β conferred to decreased p-Smad2/3 expression and also suppressed translocation of Smad4 into nuclus of B cells. Our current project is aimed to identify that MDSCs can educate normal B cells and induced a novel PD-1-PD-L1+B cell-subset, which can exert immunosuppressive functions via CyclinD-CDK4/6-pRb axis. The accomplishment of this project might extend our understanding of inhibitory immune functions of B cells in tumor microenvironment and might shed new light on anti-tumor immunity and immune therapy.