The human immune system is comprised of several types of cells that have the potential to eradicate tumors without inflicting damage on normal tissue. Over the past decade, progress in the understanding of tumor biology and immunology has offered the exciting possibility of treating malignant disease with vaccines that exploit the capacity of T cells to effectively and selectively kill tumor cells. However, the immune system frequently fails to mount a successful defense against cancers despite vaccination with tumor-associated antigens. The ability of these vaccines to generate an abundant supply of armed effector T cells is often limited by immunoregulatory signaling pathways that suppress T cell activation. In addition, many tumors create a local microenvironment that inhibits the function of T cells. The attenuation of these pathways, which facilitate the evasion of tumors from immune surveillance, thus represents a potentially effective approach for cancer immunotherapy. Specifically, it may be of interest to modify the properties of dendritic cells, T cells, and tumor cells to downregulate the expression of proteins that diminish the immune response to cancers. RNA interference (RNAi) techniques have developed into a highly effective means of intracellular gene 'knockdown' and may be successfully employed in this way to improve cancer immunotherapies. This strategy has recently been explored both in vitro and in vivo, and has generated significantly enhanced antitumor immunity in numerous studies. Nevertheless, several practical concerns remain to be resolved before RNAi technology can be implemented safely and efficiently in humans. As novel developments and discoveries in molecular biology rapidly continue to unfold, it is likely that this technology may soon translate into a potent form of gene silencing in the clinic with profound applications to cancer immunotherapy.

译文

人体免疫系统由几种类型的细胞组成,这些细胞具有消灭肿瘤而不会对正常组织造成损害的潜能。在过去的十年中,对肿瘤生物学和免疫学的理解的进步提供了利用疫苗来治疗恶性疾病的令人兴奋的可能性,这些疫苗利用了T细胞有效和选择性地杀死肿瘤细胞的能力。然而,尽管接种了肿瘤相关抗原,免疫系统却常常无法成功地防御癌症。这些疫苗产生大量供应的武装效应T细胞的能力通常受到抑制T细胞活化的免疫调节信号通路的限制。另外,许多肿瘤产生抑制T细胞功能的局部微环境。这些途径的减弱,有助于从免疫监视中逃避肿瘤,因此代表了癌症免疫疗法的潜在有效方法。具体而言,可能需要修饰树突状细胞,T细胞和肿瘤细胞的特性,以下调减弱对癌症的免疫反应的蛋白质的表达。 RNA干扰(RNAi)技术已发展成为细胞内基因“敲低”的高效手段,并且可以成功地以这种方式用于改善癌症的免疫疗法。最近已经在体外和体内研究了这种策略,并且在许多研究中已经产生了显着增强的抗肿瘤免疫性。然而,在将RNAi技术安全,有效地应用于人类之前,仍然需要解决一些实际问题。随着分子生物学的新发展和发现继续迅速发展,该技术可能很快会转化为临床上有效的基因沉默形式,并在癌症免疫疗法中得到广泛应用。

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