摘要
树突状细胞(DCs)是机体内功能最强的专职抗原递呈细胞(APCs),DCs可激发幼稚T细胞,打破肿瘤免疫耐受,引起肿瘤排斥。近年来,随着DCs的生物学特性被不断认识,DCs在肿瘤免疫、移植免疫以及抗感染方面日益受到重视。在初期的临床试验中,DCs疫苗在B细胞淋巴瘤、黑色素瘤、前列腺癌等肿瘤的治疗取得令人鼓舞的结果。然而一些免疫原性较弱的实体瘤的临床试验结果显示,DCs的疗效与期望值相差甚远。研究表明DCs受到肿瘤患者体内免疫抑制因素的影响,不能有效的激发T细胞。因此,诱导出具有对抗体内免疫抑制因素并有效递呈抗原的DCs疫苗,将会极大的推动DCs疫苗的研究进展。
一.TGF-β_1对外周血来源DCs的影响
TGF-β_1是肿瘤组织主要的免疫抑制因子之一,可以通过多种机制抑制DCs的活性,包括抗原递呈、迁移至二级淋巴器官以及致敏幼稚T细胞的能力。因此如果诱导的DCs可以有效的对抗TGF-β_1的抑制作用,必将提高DCs的疗效。本研究应用不同的细胞因子诱导DCs的成熟,通过观察诱导的DCs在添加TGF-β_1后功能状态的变化,寻找DCs诱导成熟的必须细胞因子。结果显示:(1)TGF-β_1明显抑制DCs的成熟,包括细胞表型、激发T细胞能力以及分泌IL-12的水平。(2)
DCs are the most effective professional antigen-presenting cells for priming naive T cells, and in particular they have the potential to break tumor tolerance and induce tumor-specific immune response leading to tumor rejection. With the increasing knowledge of biological characteristics of DCs, recent studies have showed that DCs are of great value in tumor immune, transplant immune, and anti-infection immune. The data from phase I / II clinical trials showed that DCs vaccine had achieved encouraging effects in B lymphoma, melanoma, prostate cancer. But when DCs vaccine was used to treat solid tumor, most of these were considered as 'weak immunogeneic' tumor, the minimal effects didn't match the expected. Studies showed that the cancer could impair the process of the priming of naive T cells by DCs. So how to induce matured DCs, which can resist the inhibitory effector of TGF-β1, is necessary in preparation of DCs vaccine. 1. The effect of TGF-β1 to PBMNC-derived dendritic cellsTGF-β1 is one of major immune inhibitory factors present in tumor microenviroment, which has been demonstrated to impair DCs functions, including presentation of antigen, stimulatation of tumor-sensitized T lymphocytes, and migratation to draining lymph nodes. So effective DCs vaccine which can counteract the inhibitory of TGF-β1 will facilitate curative effect. Here we evaluate the change of DCs ability after induce
引文
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