Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma
文献类型：期刊论文
| 作者 | Cheng, Yifei14,15; Chen, Xiaofang11,12,13; Feng, Li10; Yang, Zhicheng8,9; Xiao, Liyun12,13; Xiang, Bin7; Wang, Xiaodong6; Liu, Dongbin12,13; Lin, Penghui12,13; Shi, Jieyi14,15 |
| 刊名 | CELL DISCOVERY
 |
| 出版日期 | 2025-01-28 |
| 卷号 | 11期号:1页码:24 |
| DOI | 10.1038/s41421-024-00747-z |
| 英文摘要 | Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis. We discovered two functional units, one is the intratumor inflammatory hub featured by CAF-FAP plus CD8_PDCD1 proximity and the other is the marginal wound-healing hub with CAF-C7 plus Macrophage_SPP1 co-localization. Inhibiting CAF-FAP combined with anti-PD-1 in orthotopic HCC models led to improved tumor regression than either monotherapy. Collectively, our findings suggest stroma-targeted strategies for HCC based on defined stromal archetypes, raising the concept that CAFs change their transcriptional program and intercellular crosstalk according to the spatial context. |
| WOS关键词 | ACTIVATION PROTEIN ; T-CELLS ; IMMUNE CELLS ; LANDSCAPE ; RESISTANCE ; ANTITUMOR ; REVEALS ; IMMUNOTHERAPY ; ENCAPSULATION ; PROGNOSIS |
| 资助项目 | National Natural Science Foundation of China (National Science Foundation of China)[U23A6010] ; National Natural Science Foundation of China (National Science Foundation of China)[82394450] ; National Natural Science Foundation of China (National Science Foundation of China)[82130077] ; National Natural Science Foundation of China (National Science Foundation of China)[81961128025] ; National Natural Science Foundation of China (National Science Foundation of China)[82090053] ; National Natural Science Foundation of China (National Science Foundation of China)[32370978] ; National Natural Science Foundation of China (National Science Foundation of China)[82103037] ; National Natural Science Foundation of China (National Science Foundation of China)[82172860] ; National Natural Science Foundation of China (National Science Foundation of China)[82203643] ; National Natural Science Foundation of China[2020YFA0509000] ; National Natural Science Foundation of China[2022YFA1302902] ; National Key R&D Program of China[19XD1420700] ; National Key R&D Program of China[2018SHZDZX05] ; National Key R&D Program of China[20XD1424900] ; National Key R&D Program of China[22YF1407200] ; Science and Technology Commission of Shanghai Municipality[SZSM202003009] ; Sanming Project of Medicine in Shenzhen[2020B1212070028] ; Guangdong Provincial Key Laboratory of Human Disease Genomics ; China National GeneBank |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001407107100001 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315944]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, Qiang; Zhou, Hu; Sun, Yidi; Wu, Kui; Fan, Jia |
| 作者单位 | 1.BGI Res, Qingdao, Shandong, Peoples R China 2.BGI Genom, Inst Intelligent Med Res IIMR, Shenzhen, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Immun & Infect, Ctr Microbes Dev & Hlth, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China 4.BGI Res, Guangdong Prov Key Lab Genome Read & Write, Shenzhen, Guangdong, Peoples R China 5.Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai, Peoples R China 6.Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R China 7.Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Key Lab Computat Biol, Shanghai, Peoples R China 8.Univ Chinese Acad Sci, Beijing, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, State Key Lab Drug Res, Shanghai, Peoples R China 10.Chinese Acad Sci, Ctr Excellence Brain Sci & Intelligence Technol, State Key Lab Neurosci, Key Lab Primate Neurobiol,Inst Neurosci, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Yifei,Chen, Xiaofang,Feng, Li,et al. Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma[J]. CELL DISCOVERY,2025,11(1):24. |
| APA | Cheng, Yifei.,Chen, Xiaofang.,Feng, Li.,Yang, Zhicheng.,Xiao, Liyun.,...&Fan, Jia.(2025).Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.CELL DISCOVERY,11(1),24. |
| MLA | Cheng, Yifei,et al."Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma".CELL DISCOVERY 11.1(2025):24. |
入库方式： OAI收割
来源：上海药物研究所
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