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癌症中的免疫逃逸:机制基础与治疗策略。

Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

机构信息

Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, United States.

Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States.

出版信息

Semin Cancer Biol. 2015 Dec;35 Suppl:S185-S198. doi: 10.1016/j.semcancer.2015.03.004. Epub 2015 Mar 25.

Abstract

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.

摘要

癌症免疫逃逸是设计有效抗癌治疗策略的主要障碍。尽管在理解癌症如何逃避破坏性免疫方面已经取得了相当大的进展,但对抗肿瘤逃逸的措施并没有跟上。尽管宿主免疫系统正常,但仍有许多因素导致肿瘤持续存在。免疫编辑是肿瘤逃避监测的一个关键方面,它使肿瘤在患者体内潜伏数年,通过“平衡”和“衰老”,然后重新出现。此外,肿瘤还利用几种免疫过程,如靶向调节性 T 细胞功能或其分泌、抗原呈递、修饰免疫抑制介质的产生、耐受和免疫偏差。除此之外,肿瘤异质性和转移也在肿瘤生长中起着关键作用。已经设计了许多潜在的靶点,如促进 Th1、NK 细胞、γδ T 细胞反应,抑制 Treg 功能,诱导 IL-12 的产生,使用包括植物化学物质在内的药物,以取得对抗肿瘤进展的巨大成功。一些天然药物和植物化学物质值得进一步研究。例如,某些来自蘑菇和植物的关键多糖成分的使用已被证明对肿瘤引起的遗传不稳定性、抗生长信号、复制性永生、代谢失调等具有治疗作用。在这篇综述中,我们将讨论在理解癌症免疫逃逸基础方面取得的进展,并总结已经开发或正在研究的各种治疗措施和靶点的疗效,以增强肿瘤排斥。

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