Elluru Sri Ramulu, Duong van Huyen Jean-Paul, Delignat Sandrine, Kazatchkine Michel D, Friboulet Alain, Kaveri Srini V, Bayry Jagadeesh
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris6, UMR S 872, Paris, 75006, France.
BMC Cancer. 2008 Jun 4;8:161. doi: 10.1186/1471-2407-8-161.
Viscum album (VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression.
Four day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 microg/ml for 48 hrs. The expression of surface molecules was analyzed by flow cytometry. The ability of Qu Spez-educated DC to stimulate T cells was analyzed by allogeneic mixed lymphocyte reaction and activation of Melan-A/MART-1-specific M77-80 CD8+T cells. Cytokines in cell free culture supernatant was analyzed by cytokine bead array assay.
VA Qu Spez stimulated DCs presented with increased expression of antigen presenting molecule HLA-DR and of co-stimulatory molecules CD40, CD80 and CD86. The VA Qu Spez also induced the secretion of inflammatory cytokines IL-6 and IL-8. Further, Qu Spez-educated DC stimulated CD4+T cells in a allogeneic mixed lymphocyte reaction and activated melanoma antigen Melan-A/MART-1-specific M77-80 CD8+T cells as evidenced by increased secretion of TNF-alpha and IFNgamma.
The VA preparations stimulate the maturation and activation of human DCs, which may facilitate anti-tumoral immune responses. These results should assist in understanding the immunostimulatory properties of VA preparations and improving the therapeutic strategies.
欧洲槲寄生制剂已被用作癌症的辅助治疗。除了具有细胞毒性外,它们还被证明具有免疫刺激特性。在本研究中,我们检验了欧洲槲寄生制剂诱导人树突状细胞(DC)活化从而促进有效肿瘤消退的假说。
用5、10和15微克/毫升的欧洲槲寄生提取物(VA Qu Spez)处理4日龄单核细胞衍生的未成熟DC,处理48小时。通过流式细胞术分析表面分子的表达。通过异体混合淋巴细胞反应以及黑素瘤抗原A/MART-1特异性M77-80 CD8+T细胞的活化,分析经VA Qu Spez处理的DC刺激T细胞的能力。通过细胞因子微珠阵列分析无细胞培养上清液中的细胞因子。
VA Qu Spez刺激的DC呈现出抗原呈递分子HLA-DR以及共刺激分子CD40、CD80和CD86表达增加。VA Qu Spez还诱导炎性细胞因子IL-6和IL-8的分泌。此外,经VA Qu Spez处理的DC在异体混合淋巴细胞反应中刺激CD4+T细胞,并激活黑素瘤抗原Melan-A/MART-1特异性M77-80 CD8+T细胞,TNF-α和IFNγ分泌增加证明了这一点。
欧洲槲寄生制剂刺激人DC的成熟和活化,这可能促进抗肿瘤免疫反应。这些结果应有助于理解欧洲槲寄生制剂的免疫刺激特性并改进治疗策略。