title: Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer.
abstract: A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.
authors.affiliation: Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Jiandong
authors.initials: J
authors.lastname: Yang
authors.forename: Qinyou
authors.initials: Q
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Jingyue
authors.initials: J
authors.lastname: Yang
authors.forename: Zhaocai
authors.initials: Z
authors.lastname: Yu
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Wu
authors.forename: Hengjun
authors.initials: H
authors.lastname: Shi
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004317:Doxorubicin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D061986:MCF-7 Cells
chemical_list: D000903:Antibiotics, Antineoplastic; D019496:Cancer Vaccines; D004317:Doxorubicin; D007371:Interferon-gamma