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靶向蛋白激酶有益于癌症免疫疗法。

Targeting protein kinases benefits cancer immunotherapy.

机构信息

Department of Urology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China; Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.

Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.

出版信息

Biochim Biophys Acta Rev Cancer. 2022 Jul;1877(4):188738. doi: 10.1016/j.bbcan.2022.188738. Epub 2022 Jun 2.

Abstract

Small-molecule kinase inhibitors have been well established and successfully developed in the last decades for cancer target therapies. However, intrinsic or acquired drug resistance is becoming the major barrier for their clinical application. With the development of immunotherapies, in particular the discovery of immune checkpoint inhibitors (ICIs), the combination of ICIs with other therapies have recently been extensively explored, among which combination of ICIs with kinase inhibitors achieves promising clinical outcome in a plethora of cancer types. Here we comprehensively summarize the potent roles of protein kinases in modulating immune checkpoints both in tumor and immune cells, and reshaping tumor immune microenvironments by evoking innate immune response and neoantigen generation or presentation. Moreover, the clinical trial and approval of combined administration of kinase inhibitors with ICIs are collected, highlighting the precise strategies to benefit cancer immune therapies.

摘要

小分子激酶抑制剂在过去几十年中已被广泛应用于癌症的靶向治疗,并取得了显著的成效。然而,内在或获得性药物耐药性已成为其临床应用的主要障碍。随着免疫疗法的发展,特别是免疫检查点抑制剂(ICIs)的发现,ICIs 与其他疗法的联合应用最近得到了广泛的探索,其中包括 ICI 与激酶抑制剂的联合应用在多种癌症类型中取得了有前景的临床效果。在这里,我们全面总结了蛋白激酶在调节肿瘤和免疫细胞中的免疫检查点以及通过引发先天免疫反应和新生抗原的产生或呈递重塑肿瘤免疫微环境方面的重要作用。此外,我们还收集了激酶抑制剂与 ICI 联合应用的临床试验和批准情况,突出了使癌症免疫治疗受益的精确策略。

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