Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer
文献类型：期刊论文
| 作者 | Zhu, Qingchen3; Zhang, Guiheng3; Cao, Ming2; Huang, Huan3; He, Dan1; Zang, Zhongsheng1; Xing, Jing7; Zhan, Ming4; Pei, Siyu3; Deng, Xiuyu3 |
| 刊名 | NATURE IMMUNOLOGY
 |
| 出版日期 | 2025-05-01 |
| 卷号 | 26期号:5页码:46 |
| ISSN号 | 1529-2908 |
| DOI | 10.1038/s41590-025-02126-6 |
| 英文摘要 | Sex disparities have been epidemiologically demonstrated in non-reproductive cancers, yet how the sex-specific intrinsic microbiome orchestrates the immune system to affect these disparities is unclear. Here we identify a subpopulation of RETNLG+LCN2+ senescence-like neutrophils (RLSNs) that preferentially accumulate in the male tumor microenvironment and exert a strong immunosuppressive effect to limit antitumor immunity, resulting in poor prognosis for patients with bladder cancer. This difference in enrichment of RLSNs between sexes can be attributed to intestinal bacterium Alistipes shahii, which preferentially populates in females rather than males. A. shahii-associated metabolite lurasidone directly targets iron sequestrator LCN2 in RLSNs. By freeing Fe2+, lurasidone induces ferroptosis, thereby eliminating RLSNs and promoting antitumor immunity in females. In males lacking A. shahii and lurasidone, RLSNs have a survival advantage. Together, these findings demonstrate that a microbiota-lurasidone-LCN2 circuit regulates sexual disparity in bladder cancer and indicates the therapeutic potential of lurasidone for male cancer patients. |
| WOS关键词 | MYELOID CELLS ; LIPOCALIN-2 ; LURASIDONE ; INFECTION ; STEMNESS ; AGE |
| 资助项目 | CAS Project for Young Scientists in Basic Research[YSBR-076] ; National Natural Science Foundation of China[82425026] ; National Natural Science Foundation of China[82030041] ; National Natural Science Foundation of China[82441041] ; National Natural Science Foundation of China[82201924] ; National Natural Science Foundation of China[82425103] ; National Natural Science Foundation of China[82202932] ; National Natural Science Foundation of China[32025022] ; National Natural Science Foundation of China[32230062] ; National Key RAMP ; D Program of China[2024YFA1803103] ; National Key RAMP ; D Program of China[2018YFA0902703] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB39030300] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0480000] ; Jiangsu Cancer Hospital[YSPY202402] ; Jiangsu Natural Science Foundation[BK20220735] ; CAS Key Laboratory of Tissue Microenvironment ; Chinese Academy of Sciences ; NovelBio Co., Ltd. |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| WOS记录号 | WOS:001464473000001 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317419]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Chenli; Qin, Jun; Xiao, Yichuan |
| 作者单位 | 1.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China 2.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Urol, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China 4.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Core Lab Med Ctr Clin Res, State Key Lab Med Genom,Sch Med, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Shanghai Inst Immun & Infect, Ctr Microbes Dev & Hlth, CAS Key Lab Mol Virol & Immunol, Shanghai, Peoples R China 6.Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Canc Hosp, Dept Radiotherapy,Jiangsu Inst Canc Res, Nanjing, Peoples R China 7.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Drug Discovery & Design Ctr, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Qingchen,Zhang, Guiheng,Cao, Ming,et al. Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer[J]. NATURE IMMUNOLOGY,2025,26(5):46. |
| APA | Zhu, Qingchen.,Zhang, Guiheng.,Cao, Ming.,Huang, Huan.,He, Dan.,...&Xiao, Yichuan.(2025).Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer.NATURE IMMUNOLOGY,26(5),46. |
| MLA | Zhu, Qingchen,et al."Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer".NATURE IMMUNOLOGY 26.5(2025):46. |
入库方式： OAI收割
来源：上海药物研究所
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