标题：CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function
作者：Chen, Xi; Shao, Qianqian; Hao, Shengnan; Zhao, Zhonghua; Wang, Yang; Guo, Xiaofan; He, Ying; Gao, Wenjuan; Mao, Haiting
作者机构：[Chen, Xi; Shao, Qianqian; Hao, Shengnan; Zhao, Zhonghua; Wang, Yang; He, Ying; Gao, Wenjuan; Mao, Haiting] Shandong Univ, Qi Lu Hosp, Inst Basic Med 更多
通讯作者地址：[Mao, HT]Shandong Univ, Qi Lu Hosp, Inst Basic Med Sci, Jinan 250012, Shandong, Peoples R China.
关键词：breast cancer cell; CTLA-4; dendritic cell; CD4(+)T cell; CD8(+)T cell
摘要：Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4(+) breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4(+)/CD8(+) T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs). However, CTLA-4 blockade in breast cancer cells could recover DC maturation and cytokine production, elevate antigenpresenting function of DCs, reverse Th1/CTLs response and cytokine secretion. Subsequent study demonstrated that the activation of extracellular-signal regulated kinase and signal transducer and activator of transcription 3 of DCs caused by CTLA-4(+) breast cancer cells were the predominant mechanism of DC suppression. In addition, CTLA-4 blockade treatment also directly inhibited proliferation and induced apoptosis of CTLA-4(+) breast cancer cells. Collectively, CTLA-4 was expressed and functional on human breast cancer cells through influencing maturation and function of DCs in vitro, and CTLA-4 blockage not only recovered the antigen-presenting function of DCs and T-cells activation but also suppressed the biological activity of breast cancer cells themselves. This study highlights the clinical application of CTLA-4 blockade therapy in breast cancer.