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目的观察前列腺素E2(PGE2)对体外培养的乳腺癌抗原负载小鼠树突状细胞(DC) 迁移能力及抗乳腺癌免疫作用的影响。方法用重组小鼠粒细胞巨噬细胞集落刺激因子和重组小鼠白细胞介素-4培养BALB／c小鼠骨髓来源DC,负载乳腺癌抗原后加入PGE2,进行表型、 CCR7mRNA及蛋白、同种异体混合淋巴细胞反应、特异性淋巴细胞(CTL)杀伤活性测定。将TM40D 接种于小鼠左侧胸壁皮下制作乳腺癌动物模型,1周后皮下接种PGE2组及对照组DC,观察肿瘤抑制状况。结果体外实验显示,PGE2不影响DC的刺激淋巴细胞增殖能力和同种异体特异性杀伤活性。与对照组DC相比,PGE2培养组DC的CD80、CD86阳性细胞数增多,CCR7mRNA和蛋白表达上调(P<0．05)。体外趋化试验显示,PGE2使DC对其配体CCL19和CCL21反应性增强(P<0．05)。在乳腺癌动物模型中,PGE2培养组DC抑制肿瘤生长作用优于对照组。结论 PGE2可以通过促进 DC成熟并促进其体内迁移能力,提高抗乳腺癌DC疫苗的功效。
Objective To investigate the effect of prostaglandin E2 (PGE2) on the migration of dendritic cells (DCs) loaded with breast cancer antigen in vitro and the anti-breast cancer immune effect. Methods BALB / c mouse bone marrow-derived DCs were cultured with recombinant mouse granulocyte-macrophage colony-stimulating factor and recombinant mouse interleukin-4 and PGE2 was loaded after loading breast cancer antigen. Phenotypic, CCR7 mRNA and protein, Heterogeneous mixed lymphocyte reaction, Specific lymphocyte (CTL) activity assay. TM40D mice were inoculated subcutaneously in the left chest wall to make animal model of breast cancer. One week later, PGE2 group and control group were subcutaneously inoculated with DC to observe tumor inhibition. Results In vitro experiments showed that PGE2 did not affect the ability of DC to stimulate lymphocyte proliferation and allogeneic specific killing activity. Compared with the control group, the number of CD80 and CD86 positive cells in the PGE2 group increased and the expression of CCR7 mRNA and protein increased (P <0.05). In vitro chemotaxis assays showed that PGE2 enhanced DC reactivity to its ligands CCL19 and CCL21 (P <0.05). In the animal model of breast cancer, DCs in PGE2 group had better effect of inhibiting tumor growth than the control group. Conclusion PGE2 can enhance the efficacy of anti-breast cancer DC vaccine by promoting DC maturation and promoting its in vivo migration ability.