PMID- 29928442 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230926 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 16 IP - 1 DP - 2018 Jul TI - A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell-dendritic cell-based vaccine. PG - 529-535 LID - 10.3892/ol.2018.8631 [doi] AB - 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 (MHC)-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 ELISA. 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. FAU - Abdellateif, Mona S AU - Abdellateif MS AD - Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11976, Egypt. FAU - Shaarawy, Sabry M AU - Shaarawy SM AD - Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11976, Egypt. FAU - Kandeel, Eman Z AU - Kandeel EZ AD - Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo 11976, Egypt. FAU - El-Habashy, Ahmed H AU - El-Habashy AH AD - Department of Pathology, National Cancer Institute, Cairo University, Cairo 11976, Egypt. FAU - Salem, Mohamed L AU - Salem ML AD - Department of Zoology, Faculty of Science, Tanta University, Tanta, Gharbia 31511, Egypt. FAU - El-Houseini, Motawa E AU - El-Houseini ME AD - Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11976, Egypt. LA - eng PT - Journal Article DEP - 20180504 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC6006460 OTO - NOTNLM OT - Foxp3 OT - MCF-7 breast cancer cells OT - breast cancer OT - cytotoxic T-lymphocyte OT - dendritic cells OT - interferon-gamma OT - interleukin 12 OT - lactate dehydrogenase EDAT- 2018/06/22 06:00 MHDA- 2018/06/22 06:01 PMCR- 2018/05/04 CRDT- 2018/06/22 06:00 PHST- 2017/03/17 00:00 [received] PHST- 2017/11/16 00:00 [accepted] PHST- 2018/06/22 06:00 [entrez] PHST- 2018/06/22 06:00 [pubmed] PHST- 2018/06/22 06:01 [medline] PHST- 2018/05/04 00:00 [pmc-release] AID - OL-0-0-8631 [pii] AID - 10.3892/ol.2018.8631 [doi] PST - ppublish SO - Oncol Lett. 2018 Jul;16(1):529-535. doi: 10.3892/ol.2018.8631. Epub 2018 May 4.