NRF2在癌症中的免疫生物学：对免疫治疗和治疗靶向的影响。

IF 7.3 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Oncogene Pub Date : 2025-09-13 DOI:10.1038/s41388-025-03560-4

Harit Panda, Natalie G. Rowland, Caroline M. Krall, Brittany M. Bowman, Michael B. Major, Paul Zolkind

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引用次数: 0

摘要

核因子红细胞2相关因子2 （NRF2）是一种转录因子，在细胞防御氧化应激和外源生物机制中起关键调节作用。NRF2调节200多个基因的表达，这些基因与抗氧化反应、药物代谢和细胞恢复能力有关。NRF2的组成性激活是癌症中常见的事件，最近的进展为NRF2在肿瘤发生、免疫逃避和治疗抵抗中的作用提供了令人瞩目的见解。这篇综述旨在全面概述NRF2在塑造肿瘤免疫微环境中的作用及其对临床结果和治疗机会的影响。在多种肿瘤亚型中，NRF2的激活与抗pd1免疫治疗的反应受损有关。来自基因工程小鼠模型、体外研究和临床试验样本的机制见解表明，NRF2活性如何支持细胞弹性，减少细胞毒性免疫反应，并促进代谢重编程。这也提供了一个可以通过新型药物治疗靶向的脆弱性，未来的方向将包括开发针对肿瘤依赖性的最佳组合策略，同时最大限度地减少毒性和全身脱靶免疫相关效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting

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NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting

Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that acts as a key regulator in cellular defense mechanisms against oxidative stress and xenobiotics. NRF2 modulates the expression of over 200 genes involved in antioxidant response, drug metabolism, and cellular resilience. Constitutive activation of NRF2 is a common event in cancer and recent advances provide remarkable insights into the role of NRF2 in oncogenesis, immune evasion, and treatment resistance. This review aims to provide a comprehensive overview of the role of NRF2 in shaping the tumor immune microenvironment and the impact this has on clinical outcomes and treatment opportunities. Across multiple tumor subtypes, the activation of NRF2 is associated with impaired responses to anti-PD1 immunotherapy. Mechanistic insights from genetically engineered mouse models, in vitro studies, and clinical trial samples demonstrate how NRF2 activity supports cell resiliency, diminishes cytotoxic immune responses, and promotes metabolic reprogramming. This also provides a vulnerability which can be targeted through novel drug therapy and future directions will include development of optimal combination strategies to target tumor dependencies while minimizing toxicity and systemic off-target immune related effects.

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来源期刊

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.