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基于树突状细胞的疫苗接种方法与化疗药物联合使用的原理。

Rationale for the Combination of Dendritic Cell-Based Vaccination Approaches With Chemotherapy Agents.

作者信息

Truxova I, Hensler M, Skapa P, Halaska M J, Laco J, Ryska A, Spisek R, Fucikova J

机构信息

2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic; Sotio a.s., Prague, Czech Republic.

Sotio a.s., Prague, Czech Republic.

出版信息

Int Rev Cell Mol Biol. 2017;330:115-156. doi: 10.1016/bs.ircmb.2016.09.003. Epub 2016 Nov 29.

DOI:10.1016/bs.ircmb.2016.09.003
PMID:28215530
Abstract

Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death. Moreover, they may support DC-induced adaptive immune responses by disrupting tumor-induced immunosuppressive mechanisms via selective depletion or inhibition of regulatory subsets, such as myeloid-derived suppressor cells and/or regulatory T cells (Tregs). Here, we summarize our current knowledge on the capacity of anticancer chemotherapeutics to modulate DC phenotype and functions and the results of ongoing clinical trials evaluating the use of DC-based immunotherapy in combination with chemotherapy in cancer patients.

摘要

由于树突状细胞(DCs)在抗肿瘤免疫的启动和调节中发挥核心作用,其已被广泛用于癌症免疫治疗的测试。尽管有一些令人鼓舞的临床应用,但现有的基于DC的免疫治疗效果并不一致。最近的研究已经确定了一些策略,这些策略可能使基于DC的疫苗更有效,例如与有可能协同增强DC功能的抗肿瘤药物联合使用。某些细胞毒性药物可以通过直接促进DC成熟或通过诱导免疫原性肿瘤细胞死亡来刺激DC。此外,它们可以通过选择性清除或抑制调节性亚群(如髓源性抑制细胞和/或调节性T细胞(Tregs))来破坏肿瘤诱导的免疫抑制机制,从而支持DC诱导的适应性免疫反应。在此,我们总结了目前关于抗癌化疗药物调节DC表型和功能能力的知识,以及正在进行的评估基于DC的免疫治疗与化疗联合用于癌症患者的临床试验结果。

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