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Sci.Rep:四川大学魏于全研究员发表抗肿瘤研究文章

作者:魏于全 发布时间:2015-11-30

 日前,自然出版集团旗下综合类刊物《Scientific Reports》在线发表了四川大学魏于全研究员发表的一项研究,文章指出尿酸能够增强树突状细胞瘤苗的抗肿瘤免疫。

树突状细胞(DC)是机体内功能最强的抗原提呈细胞(APC),也是唯一能够刺激初始免疫应答的APC,在对肿瘤产生主动免疫上起着重要的作用:它摄取、加工肿瘤抗原,通过主要组织相容性复合物MHC-II提呈,进而激活初始T细胞,使机体对肿瘤产生主动免疫。因此,近年来树突状细胞瘤苗成为了肿瘤免疫治疗的研究热点。然而,尽管这些树突状细胞瘤苗具有相当大的优势,但在某些情况下仍然只能发挥有效的抗肿瘤效应,因此需要添加一些佐剂来激发强烈且持久的免疫反应。

UA是嘌呤代谢信号通路的一种天然产物,濒死细胞将其释放出来,最终生成结晶。研究报道,结晶UA可通过提高共刺激分子CD80和CD86表达来刺激树突状细胞成熟,增强T细胞对外源抗原的反应。研究证实,结晶UA可激活巨噬细胞生成一些炎症介质,它有可能以一种相似的方式刺激了树突状细胞。新研究中四川大学的研究人员利用了UA作为树突状细胞瘤苗的一种佐剂,发现给予UA可大大提高肿瘤溶解物冲击的树突状细胞瘤苗延缓肿瘤生长的能力。研究人员是通过过继转输的淋巴细胞来达到这种抗瘤活性的,CD8+ T细胞和NK细胞是获得有效免疫的必要条件。他们证实这增加了活化CD8+ T细胞累积,并提高了IFN-γ的生成。

新研究证实,给予UA可提高肿瘤溶解物冲击的树突状细胞瘤苗的抗肿瘤活性,由此,为将UA应用于树突状细胞瘤苗治疗策略提供了理论基础。

原文链接:

Uric acid enhances the antitumor immunity of dendritic cell-based vaccine

原文摘要:

Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8+ T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8+ T cells and an elevated production of IFN-γ. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies.

文章来源:生物帮