Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade
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 impac...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-024-02197-3 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xiaofeng Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b98d968b5fbd4a44b969fcf1ce4ee01a |
| institution | DOAJ |
| issn | 1476-4598 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-b98d968b5fbd4a44b969fcf1ce4ee01a2025-08-20T02:43:35ZengBMCMolecular Cancer1476-45982024-12-012311610.1186/s12943-024-02197-3Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockadeXiaofeng Li0Zhishan Zhang1Yingying Li2Lijin Chen3Yan Huang4Lijuan Su5Wenjun Xu6Yanni Hong7Jianjiao Li8Mujin Chen9Hongkui Yang10Hong Zhao11Bin Zhao12Quanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityThe Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityAbstract 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.https://doi.org/10.1186/s12943-024-02197-3KDM5Cancer immunotherapyBiomarkerTumor immunity |
| spellingShingle | 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 Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade Molecular Cancer KDM5 Cancer immunotherapy Biomarker Tumor immunity |
| title | Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade |
| title_full | Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade |
| title_fullStr | Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade |
| title_full_unstemmed | Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade |
| title_short | Mutation of lysine-specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade |
| title_sort | mutation of lysine specific demethylase 5 is associated with enhanced tumor immunity and favorable outcomes in pan cancer immune checkpoint blockade |
| topic | KDM5 Cancer immunotherapy Biomarker Tumor immunity |
| url | https://doi.org/10.1186/s12943-024-02197-3 |
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