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肿瘤诱导的逃逸机制及其与检查点抑制剂治疗耐药性的关联。

Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy.

机构信息

Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Magdeburger Straße 2, 06110, Halle (Saale), Germany.

Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.

出版信息

Cancer Immunol Immunother. 2019 Oct;68(10):1689-1700. doi: 10.1007/s00262-019-02373-1. Epub 2019 Aug 3.

Abstract

Immunotherapy aims to activate the immune system to fight cancer in a very specific and targeted manner. Despite the success of different immunotherapeutic strategies, in particular antibodies directed against checkpoints as well as adoptive T-cell therapy, the response of patients is limited in different types of cancers. This attributes to escape of the tumor from immune surveillance and development of acquired resistances during therapy. In this review, the different evasion and resistance mechanisms that limit the efficacy of immunotherapies targeting tumor-associated antigens presented by major histocompatibility complex molecules on the surface of the malignant cells are summarized. Overcoming these escape mechanisms is a great challenge, but might lead to a better clinical outcome of patients and is therefore currently a major focus of research.

摘要

免疫疗法旨在以非常特异和靶向的方式激活免疫系统来对抗癌症。尽管不同的免疫治疗策略,特别是针对检查点的抗体和过继性 T 细胞疗法取得了成功,但患者的反应在不同类型的癌症中受到限制。这归因于肿瘤逃避免疫监视以及在治疗过程中产生获得性耐药性。在这篇综述中,总结了限制针对恶性细胞表面主要组织相容性复合物分子上呈现的肿瘤相关抗原的免疫疗法疗效的不同逃逸和耐药机制。克服这些逃逸机制是一个巨大的挑战,但可能会导致患者的临床结果更好,因此目前是研究的主要重点。

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