一种基于活癌细胞-树突状细胞的疫苗增强乳腺癌患者抗肿瘤免疫反应的新型潜在有效策略。
A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell-dendritic cell-based vaccine.
作者信息
Abdellateif Mona S, Shaarawy Sabry M, Kandeel Eman Z, El-Habashy Ahmed H, Salem Mohamed L, El-Houseini Motawa E
机构信息
Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11976, Egypt.
Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo 11976, Egypt.
出版信息
Oncol Lett. 2018 Jul;16(1):529-535. doi: 10.3892/ol.2018.8631. Epub 2018 May 4.
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 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 CD4CD25 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-γ (IFN-γ) 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 CD4CD25Foxp3 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-γ (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.
树突状细胞（DCs）已被用于多项癌症免疫治疗的临床试验；然而，它们在实体瘤中的成效有限。因此，本研究的目的是通过优化基于DC的活疫苗，为乳腺癌患者确定一种新的潜在免疫治疗靶点。用活的MCF-7乳腺癌细胞致敏未成熟DCs，并通过流式细胞术分析测量CD83、CD86和主要组织相容性复合体（MHC）-II的表达，以及不同的T细胞亚群，即CD4 T细胞、CD8 T细胞和CD4CD25叉头框蛋白3（Foxp3）调节性T细胞（Tregs），来评估DCs的活性和成熟度。除逆转录定量聚合酶链反应外，还通过酶联免疫吸附测定（ELISA）测量Foxp3水平。通过ELISA测定白细胞介素-12（IL-12）和干扰素-γ（IFN-γ）的水平。最后，通过ELISA测量乳酸脱氢酶（LDH）释放来评估细胞毒性T淋巴细胞（CTLs）的细胞毒性。结果表明，用乳腺癌细胞致敏后，CD83、CD86和MHC-II DCs显著升高（P<0.001）。此外，CD4和CD8 T细胞的活化增加，而CD4CD25Foxp3 Tregs显著减少（P<0.001）。此外，还发现FOXP3基因表达显著下调（P<0.001），ELISA显示其活化后蛋白质水平显著降低（P<0.001）。此外，观察到IL-12和IFN-γ的分泌显著增加（P=0.001）。LDH释放显著增加（P<0.001），表明CTLs对癌细胞具有明显的细胞毒性。因此，基于活乳腺癌细胞-DC的疫苗可能为新型乳腺癌免疫治疗开辟一条创新途径。
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