TY - JOUR
T1 - Presence of onco-fetal neighborhoods in hepatocellular carcinoma is associated with relapse and response to immunotherapy
AU - Li, Ziyi
AU - Pai, Rhea
AU - Gupta, Saurabh
AU - Currenti, Jennifer
AU - Guo, Wei
AU - Di Bartolomeo, Anna
AU - Feng, Hao
AU - Zhang, Zijie
AU - Li, Zhizhen
AU - Liu, Longqi
AU - Singh, Abhishek
AU - Bai, Yinqi
AU - Yang, Bicheng
AU - Mishra, Archita
AU - Yang, Katharine
AU - Qiao, Liang
AU - Wallace, Michael
AU - Yin, Yujia
AU - Xia, Qiang
AU - Chan, Jerry Kok Yen
AU - George, Jacob
AU - Chow, Pierce Kah Hoe
AU - Ginhoux, Florent
AU - Sharma, Ankur
N1 - Publisher Copyright:
© 2024, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Onco-fetal reprogramming of the tumor ecosystem induces fetal developmental signatures in the tumor microenvironment, leading to immunosuppressive features. Here, we employed single-cell RNA sequencing, spatial transcriptomics and bulk RNA sequencing to delineate specific cell subsets involved in hepatocellular carcinoma (HCC) relapse and response to immunotherapy. We identified POSTN + extracellular matrix cancer-associated fibroblasts (EM CAFs) as a prominent onco-fetal interacting hub, promoting tumor progression. Cell–cell communication and spatial transcriptomics analysis revealed crosstalk and co-localization of onco-fetal cells, including POSTN + CAFs, FOLR2 + macrophages and PLVAP + endothelial cells. Further analyses suggest an association between onco-fetal reprogramming and epithelial–mesenchymal transition (EMT), tumor cell proliferation and recruitment of Treg cells, ultimately influencing early relapse and response to immunotherapy. In summary, our study identifies POSTN + CAFs as part of the HCC onco-fetal niche and highlights its potential influence in EMT, relapse and immunotherapy response, paving the way for the use of onco-fetal signatures for therapeutic stratification.
AB - Onco-fetal reprogramming of the tumor ecosystem induces fetal developmental signatures in the tumor microenvironment, leading to immunosuppressive features. Here, we employed single-cell RNA sequencing, spatial transcriptomics and bulk RNA sequencing to delineate specific cell subsets involved in hepatocellular carcinoma (HCC) relapse and response to immunotherapy. We identified POSTN + extracellular matrix cancer-associated fibroblasts (EM CAFs) as a prominent onco-fetal interacting hub, promoting tumor progression. Cell–cell communication and spatial transcriptomics analysis revealed crosstalk and co-localization of onco-fetal cells, including POSTN + CAFs, FOLR2 + macrophages and PLVAP + endothelial cells. Further analyses suggest an association between onco-fetal reprogramming and epithelial–mesenchymal transition (EMT), tumor cell proliferation and recruitment of Treg cells, ultimately influencing early relapse and response to immunotherapy. In summary, our study identifies POSTN + CAFs as part of the HCC onco-fetal niche and highlights its potential influence in EMT, relapse and immunotherapy response, paving the way for the use of onco-fetal signatures for therapeutic stratification.
UR - http://www.scopus.com/inward/record.url?scp=85181204808&partnerID=8YFLogxK
U2 - 10.1038/s43018-023-00672-2
DO - 10.1038/s43018-023-00672-2
M3 - Article
AN - SCOPUS:85181204808
SN - 2662-1347
VL - 5
SP - 167
EP - 186
JO - Nature Cancer
JF - Nature Cancer
IS - 1
ER -