A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell-dendritic cell-based vaccine

作者：Abdellateif Mona S^*; Shaarawy Sabry M; Kandeel Eman Z; El Habashy Ahmed H; Salem Mohamed L; El Houseini Motawa E

来源：Oncology Letters, 2018, 16(1): 529-535.

DOI：10.3892/ol.2018.8631

• breast cancer
• dendritic cells
• Foxp3
• lactate dehydrogenase
• cytotoxic T-lymphocyte
• interleukin 12
• interferon-gamma
• MCF-7 breast cancer cells

Dendritic cells (DCs) have been used in a number of clinical trials for cancer immunotherapy; however, they have achieved limited success in solid tumors. Consequently the aim of the present study was to identify a novel potential immunotherapeutic target for breast cancer patients through in vitro optimization of a viable DC-based vaccine. Immature DCs were primed by viable MCF-7 breast cancer cells and the activity and maturation of DCs were assessed through measuring CD83, CD86 and major histocompatibility complex (MTIC)-II expression, in addition to different T cell subpopulations, namely CD4(+) T cells, CD8(+ )T cells, and CD4(+)CD25(+) forkhead box protein 3 (Foxp3)(+) regulatory T cells (Tregs), by flow cytometric analysis. Foxp3 level was also measured by enzyme-linked immunosorbent assay (ELISA) in addition to reverse-transcription quantitative polymerase chain reaction. The levels of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) were determined by ELISA. Finally, the cytotoxicity of cytotoxic T lymphocytes (CTLs) was evaluated through measuring lactate dehydrogenase (LDH) release by ELISA. The results demonstrated that CD83(+), CD86(+) and MHC-II+. DCs were significantly elevated (P<0.001) following priming with breast cancer cells. In addition, there was increased activation of CD4(+) and CD8(+) T-cells, with a significant decrease of CD4(+)CD25(+)Foxp3(+) Tregs (P<0.001). Furthermore, a significant downregulation of FOXP3 gene expression (P <0.001) was identified, and a significant decrease in the level of its protein following activation (P<0.001) was demonstrated by EIJSA. Additionally, significant increases in the secretion of IL-12 and IFN-gamma (P=0.001) were observed. LDH release was significantly increased (P<0.001), indicating a marked cytotoxicity of CTLs against cancer cells. Therefore viable breast cancer cell-DC-based vaccines could expose an innovative avenue for a novel breast cancer immunotherapy.

• 出版日期2018-7