Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model; Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC.
Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model; Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC.
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小鼠肺癌最小残留模型中的树突状细胞 (DC) 疫苗；单核细胞来源的 DC 与造血干细胞来源的 DC 的比较。
DOI：
10.4110/in.2012.12.6.269
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发表时间：
2012-12
期刊：
影响因子：
6
通讯作者：
Lee H
中科院分区：
文献类型：
--
作者：
Baek S;Lee SJ;Kim MJ;Lee H
研究了单核细胞来源的DC（MoDC）疫苗在具有可行但较弱的Ag特异性免疫应答和不完全阻断肿瘤生长的肺癌模型中的抗肿瘤作用。为了克服这一局限性，本研究采用小鼠肺癌微小残留模型（MRD），体外培养造血干细胞来源的DC（SDC），比较MoDC和SDC的抗肿瘤作用。从CD 34+造血干细胞与GM-CSF、SCF和IL-4培养14天（SDC）或从单核细胞与GM-CSF和IL-4培养7天（MoDC）的治疗性DC。在DC注射前一天，将DC以一周的间隔两次注射到接种有刘易斯肺癌细胞（LLC）的小鼠的腹膜中。在末次DC注射后3周观察抗肿瘤反应和免疫调节。SDC中CD 11 c表达、IL-12和TGF-β分泌较高，而MoDC中CCR 7表达、IFN-γ和IL-10分泌较高。两种DC培养物中CD 11 c + CD 8a+细胞的比例相似。虽然两种DC均能降低肿瘤负荷，但SDC治疗组的组织学抗肿瘤效应和分泌IFN-γ的CD 8 + T细胞的频率高于MoDC。因此，尽管MoDC和SDC都能诱导小鼠产生抗肿瘤免疫，但SDC可能是比MoDC更好的抗肿瘤疫苗。
The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either CD34+ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-β secretion were higher in SDC but CCR7 expression, IFN-γ and IL-10 secretion were higher in MoDC. The proportion of CD11c+CD8a+ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-γ secreting CD8+ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.