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解析 NLRP 家族:结构、功能、激活、对肿瘤进展的关键影响以及作为癌症治疗靶点的潜力。

Unraveling the NLRP family: Structure, function, activation, critical influence on tumor progression, and potential as targets for cancer therapy.

机构信息

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China; Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410013, China.

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China; Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410013, China.

出版信息

Cancer Lett. 2024 Nov 28;605:217283. doi: 10.1016/j.canlet.2024.217283. Epub 2024 Oct 2.

Abstract

The innate immune system serves as the body's initial defense, swiftly detecting danger via pattern recognition receptors (PRRs). Among these, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing proteins (NLRPs) are pivotal in recognizing pathogen-associated and damage-associated molecular patterns, thereby triggering immune responses. NLRPs, the most extensively studied subset within the NLR family, form inflammasomes that regulate inflammation, essential for innate immunity activation. Recent research highlights NLRPs' significant impact on various human diseases, including cancer. With differential expression across organs, NLRPs influence cancer progression by modulating immune reactions, cell fate, and proliferation. Their clinical significance in cancer makes them promising therapeutic targets. This review provides a comprehensive overview of the structure, function, activation mechanism of the NLRPs family and its potential role in cancer progression. In addition, we particularly focused on the concept of NLRP as a therapeutic target and its potential value in combination with immune checkpoint inhibitors.

摘要

固有免疫系统是机体的第一道防线,通过模式识别受体(PRRs)快速检测危险。其中,核苷酸结合寡聚化结构域样受体家族富含pyrin 结构域的蛋白(NLRPs)在识别病原体相关和损伤相关分子模式方面起着关键作用,从而触发免疫反应。NLRPs 是 NLR 家族中研究最广泛的亚类,它们形成炎症小体,调节炎症,这对固有免疫的激活至关重要。最近的研究强调了 NLRPs 在各种人类疾病(包括癌症)中的重要作用。NLRPs 在不同器官中的表达差异通过调节免疫反应、细胞命运和增殖来影响癌症的进展。它们在癌症中的临床意义使它们成为有前途的治疗靶点。本综述全面概述了 NLRPs 家族的结构、功能、激活机制及其在癌症进展中的潜在作用。此外,我们特别关注 NLRP 作为治疗靶点的概念及其与免疫检查点抑制剂联合应用的潜在价值。

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