髓系来源抑制细胞(MDSCs)通过抑制肿瘤浸润T淋巴细胞,诱导免疫逃逸而促进肿瘤侵袭和转移。我们前期研究发现乳腺癌组织中存在一群低分化MDSCs，其STAT3/IDO途径的异常活化介导MDSCs的T细胞免疫抑制活性，并促进乳腺癌淋巴结转移。体外实验证实炎性因子IL-6是调控MDSCs中STAT3/IDO途径异常活化的关键启动因子，但具体机制不清。本研究首先比较肿瘤源性IL-6与乳腺癌原位MDSCs数量、分布、因子释放和免疫活性之间相关性；其次围绕三个关键信号节点深入挖掘乳腺癌MDSCs中导致IL-6/STAT3/SOCS通路失调的主要分子事件，利用目标序列捕获测序、甲基化特异性PCR和基因芯片技术研究SOCS负调控障碍的分子机制；最后通过RNA干扰和基因敲除模型阐明IL-6/STAT3/SOCS通路失调对MDSCs生成和免疫活性的调控作用，并筛选抑制MDSCs和减少转移的抗乳腺癌靶向治疗。

Myeloid derived suppressor cells(MDSCs) promote cancer invasion and metastasis by inhibiting tumor infiltrated T lymphocytes and inducing immune eacape. Our previous studies demonstrated that poorly differentiated MDSCs were identified in breast cancer tissues, in which abnormal activation of the STAT3/IDO pathway mediates MDSCs-induced T cells immunosuppresion and promotes lymph node metastasis of breast cancer.Proinflammatory cytokine IL-6 was proved to be the key trigger of dysfunctional activation of the STAT3/IDO pathway in MDSCs, but the concrete mechanisms were unclear. Therefore, in this study, we will first compare the correlation between tumor-derived IL-6 and MDSCs in breast cancer tissues. Then, we will investigate the molecular events and underlying mechanisms manipulating the dysregualtion of the IL-6/STAT3/SOCS pathway. Afterward, we will elucidate the IL-6/STAT3/SOCS pathway-mediated regulation on MDSCs development and immuno- suppressive activity both in vivo and vitro using RNA interference and gene knockout models, in order to screen potential target therapies for inhibiting MDSCs and decreasing breast cancer metastasis.