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抗肿瘤免疫应答中的膜蛋白运输:内体-溶酶体系统的作用

英文原题:Membrane protein trafficking in the anti-tumor immune response: work of endosomal-lysosomal system.

查看英文原题

Membrane protein trafficking in the anti-tumor immune response: work of endosomal-lysosomal system.

PubMed 2022/12/17(内容时间) Cancer Cell Int Q1 · IF 7(JCR 2025)

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中文摘要

免疫治疗已经改变了多种癌症类型的治疗格局。近十年来,免疫治疗取得了巨大进展,包括免疫检查点抑制剂、过继性T细胞治疗和癌症疫苗。ICIs通过逆转肿瘤诱导的免疫抑制发挥作用,导致免疫系统的强烈激活和持久的免疫反应。然而,其临床应用面临若干挑战,尤其是在大多数患者中缓解率较低。随着越来越多的研究关注膜免疫检查点蛋白的转运和降解,这一过程会干扰对免疫治疗的应答,因此有必要总结调控这些跨膜结构域蛋白易位进入细胞质并通过溶酶体降解的机制。此外,其他免疫相关跨膜结构域蛋白,如T细胞受体和主要组织相容性复合体,与新抗原呈递相关。内体-溶酶体系统还可以调控膜上的TCR和新抗原-MHC复合物,从而影响过继性T细胞治疗和癌症疫苗的疗效。总之,我们讨论了免疫检查点蛋白、TCR和新抗原-MHC复合物在内体-溶酶体系统上的表面递送、内化、再循环和降解过程,以期为优化癌症免疫治疗提供生物学依据。

展开英文摘要原文

Immunotherapy has changed the treatment landscape for multiple cancer types. In the recent decade, great progress has been made in immunotherapy, including immune checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. ICIs work by reversing tumor-induced immunosuppression, resulting in robust activation of the immune system and lasting immune responses.

Whereas, their clinical use faces several challenges, especially the low response rate in most patients. As an increasing number of studies have focused on membrane immune checkpoint protein trafficking and degradation, which interferes with response to immunotherapy, it is necessary to summarize the mechanism regulating those transmembrane domain proteins translocated into the cytoplasm and degraded via lysosome.

In addition, other immune-related transmembrane domain proteins such as T-cell receptor and major histocompatibility are associated with neoantigen presentation. The endosomal-lysosomal system can also regulate TCR and neoantigen-MHC complexes on the membrane to affect the efficacy of adoptive T-cell therapy and cancer vaccines.

In conclusion, we discuss the process of surface delivery, internalization, recycling, and degradation of immune checkpoint proteins, TCR, and neoantigen-MHC complexes on the endosomal-lysosomal system in biology for optimizing cancer immunotherapy.

论文信息

作者
Jin Y、Deng Z、Zhu T
第一作者单位
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.China
通讯作者单位
Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China. zhuting_whu@outlook.com.China
文献类型
综述
期刊
Cancer cell international2022 Dec 17
原文标识
PubMed 36528587 · DOI 10.1186/s12935-022-02805-6