Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-12-27 DOI:10.1186/s12943-024-02197-3

Xiaofeng Li, Zhishan Zhang, Yingying Li, Lijin Chen, Yan Huang, Lijuan Su, Wenjun Xu, Yanni Hong, Jianjiao Li, Mujin Chen, Hongkui Yang, Hong Zhao, Bin Zhao

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Abstract

The lysine-specific demethylase 5 (KDM5) family, a key post-translational modification of chromatin, can shape tumor immune microenvironment. Here, we performed an extensive clinical and bioinformatic analysis to explore the association between KDM5 mutation and tumor immunity and its impact on the outcomes in pan-cancer immunotherapy. In 2943 patients across 12 tumor types treated with immune checkpoint inhibitors, KDM5-mutant tumors were associated with favorable overall survival (hazard ratio, 0.72; 95% confidence interval, 0.59–0.87; P = 0.004) and objective response rate (41.7% vs. 26.8%; P = 0.001). Further multi-omics analysis revealed KDM5 mutation was related to boosted tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, KDM5 mutation indicates enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade. These results have implication for treatment decision-making and developing immunotherapy for personalized care.

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赖氨酸特异性去甲基酶5的突变与肿瘤免疫增强和泛癌症免疫检查点阻断的有利结果相关

赖氨酸特异性去甲基酶5 （KDM5）家族是染色质翻译后修饰的关键，可以塑造肿瘤免疫微环境。在这里，我们进行了广泛的临床和生物信息学分析，以探索KDM5突变与肿瘤免疫之间的关系及其对泛癌症免疫治疗结果的影响。在接受免疫检查点抑制剂治疗的12种肿瘤类型的2943例患者中，kdm5突变肿瘤与有利的总生存率相关(风险比，0.72；95%置信区间为0.59-0.87；P = 0.004)和客观有效率(41.7% vs. 26.8%；p = 0.001)。进一步的多组学分析显示，KDM5突变与肿瘤免疫原性增强、免疫细胞浸润增强和免疫反应改善有关。综上所述，KDM5突变表明肿瘤免疫增强和泛肿瘤免疫检查点阻断的良好结果。这些结果对治疗决策和开发个性化护理的免疫疗法具有指导意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.