Chen Guidong, Li Xingchen, Ji Chenyan, Liu Pengpeng, Zhou Li, Xu Dechen, Wang Dong, Li Jie, Yu Jinpu
Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
Front Bioeng Biotechnol. 2022 Oct 18;10:973731. doi: 10.3389/fbioe.2022.973731. eCollection 2022.
Early myeloid-derived suppressor cells (eMDSCs) are a newly characterized subclass of MDSCs, which exhibit more potent immunosuppressive capacity than classical MDSCs. Previously, we found high eMDSCs infiltration was correlated with poor prognosis of breast cancer, though the regulatory mechanisms have not been fully understood. Here, we constructed a 21-gene signature to evaluate the status of eMDSCs infiltration within breast cancer tissues and found that highly infiltrated eMDSCs affected the prognosis of breast cancer patients, especially in luminal A subtype. We also found that eMDSCs promoted epithelial-mesenchymal transition (EMT) and accelerated cell migration and invasion . Meanwhile, eMDSCs significantly downregulated ARID1A expression in luminal A breast cancer, which was closely associated with EMT and was an important prognostic factor in breast cancer patients. Moreover, significant changes of EMT-related genes were detected in luminal A breast cancer cells after co-cultured with eMDSCs or ARID1A knock-down and overexpression of ARID1A significantly reversed this procedure. These results implied that eMDSCs might suppress the ARID1A expression to promote EMT in luminal A breast cancer cells, which might provide a new light on developing novel treatment regimens for relapsed luminal A breast cancer after conventional therapies.
早期髓系来源抑制细胞（eMDSCs）是髓系来源抑制细胞（MDSCs）新鉴定出的一个亚类，其免疫抑制能力比经典MDSCs更强。此前，我们发现eMDSCs的高浸润与乳腺癌的不良预后相关，尽管其调控机制尚未完全明确。在此，我们构建了一个21基因特征来评估乳腺癌组织中eMDSCs的浸润状态，发现高浸润的eMDSCs影响乳腺癌患者的预后，尤其是在腔面A型亚型中。我们还发现eMDSCs促进上皮-间质转化（EMT）并加速细胞迁移和侵袭。同时，eMDSCs显著下调腔面A型乳腺癌中ARID1A的表达，这与EMT密切相关，并且是乳腺癌患者的一个重要预后因素。此外，与eMDSCs共培养或敲低ARID1A后，在腔面A型乳腺癌细胞中检测到EMT相关基因的显著变化，而ARID1A的过表达显著逆转了这一过程。这些结果表明，eMDSCs可能通过抑制ARID1A的表达来促进腔面A型乳腺癌细胞中的EMT，这可能为开发针对传统治疗后复发的腔面A型乳腺癌的新型治疗方案提供新的思路。
