title: CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function.
abstract: 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 antigen-presenting 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.
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Hao
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute of Basic Medicial Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, 250012, P.R.China.
authors.forename: Haiting
authors.initials: H
authors.lastname: Mao
mesh_terms: D017951:Antigen Presentation; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D061986:MCF-7 Cells; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines
keywords: CD4+T cell; CD8+T cell; CTLA-4; breast cancer cell; dendritic cell