Li Xiaofeng, Zhang Zhishan, Li Yingying, Chen Lijin, Huang Yan, Su Lijuan, Xu Wenjun, Hong Yanni, Li Jianjiao, Chen Mujin, Yang Hongkui, Zhao Hong, Zhao Bin
Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.
Second Affiliated Hospital, Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
Mol Cancer. 2024 Dec 27;23(1):281. doi: 10.1186/s12943-024-02197-3.
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.
赖氨酸特异性去甲基化酶5（KDM5）家族是染色质的一种关键翻译后修饰，可塑造肿瘤免疫微环境。在此，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联及其对泛癌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突变型肿瘤与良好的总生存期（风险比，0.72；95%置信区间，0.59 - 0.87；P = 0.004）和客观缓解率（41.7%对26.8%；P = 0.001）相关。进一步的多组学分析表明，KDM5突变与增强的肿瘤免疫原性、免疫细胞浸润增加和免疫反应改善有关。总之，KDM5突变表明在泛癌免疫检查点阻断中肿瘤免疫增强和预后良好。这些结果对治疗决策和开发个性化免疫治疗具有启示意义。
