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树突状细胞呈递肿瘤抗原及面临的挑战。

Presentation of tumour antigens by dendritic cells and challenges faced.

机构信息

School of Biological Sciences, The University of Edinburgh, Edinburgh, Scotland, United Kingdom.

出版信息

Curr Opin Immunol. 2010 Feb;22(1):137-44. doi: 10.1016/j.coi.2010.01.002. Epub 2010 Jan 29.

Abstract

The use of dendritic cells (DCs) for the generation of anti-tumour immunity has been the focus of a vast array of scientific and clinical studies. The ability of DCs to present protein tumour antigens (T-Ags) to CD4(+) and CD8(+) T cells is pivotal to the success of therapeutic cancer vaccines. DC's specialised capacity to cross-present exogenous Ags onto major histocompatibility (MHC) class I molecules for the generation of T-Ag-specific cytotoxic T lymphocytes (CTLs) has made these cells the focal point of vaccine-based immunotherapy of cancer. However, although DC-based strategies can induce T cell responses in cancer patients, recent reviews of clinical studies demonstrate that DC-based approaches have essentially failed to meet their clinical end points. These findings highlight the need to re-evaluate the DC-based vaccine strategies and incorporate recent advancements in DC biology and tumour immunology. The current review considers the issues related to how best to target the Ag-processing pathway of DCs, the role of adjuvants, the appropriate conditioning of the DCs and strategies to overcome tumour-mediated immune escape.

摘要

树突状细胞(DCs)在抗肿瘤免疫中的应用一直是大量科学和临床研究的重点。DC 向 CD4(+)和 CD8(+)T 细胞呈递蛋白肿瘤抗原(T-Ags)的能力对于治疗性癌症疫苗的成功至关重要。DC 能够将外源性 Ag 交叉呈递给主要组织相容性(MHC)I 类分子,以产生 T-Ag 特异性细胞毒性 T 淋巴细胞(CTLs),这使得这些细胞成为癌症基于疫苗的免疫治疗的焦点。然而,尽管基于 DC 的策略可以在癌症患者中诱导 T 细胞反应,但最近对临床研究的综述表明,基于 DC 的方法基本上未能达到其临床终点。这些发现强调需要重新评估基于 DC 的疫苗策略,并纳入 DC 生物学和肿瘤免疫学的最新进展。本综述考虑了如何最好地靶向 DC 的 Ag 处理途径、佐剂的作用、DC 的适当调理以及克服肿瘤介导的免疫逃逸的策略等问题。

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