Inhibition of ACLY enhances tumor immunogenicity and resolves MASH-driven HCC
Immunosuppressive tumor microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma. To further investigate tumor–immune interactions, we performed spatial transcriptomics on livers from MASH-driven HCC mouse models (WD-DEN, WT or Acly KO mice and from WD-CCL4, Vehicle, or EVT0185 (100mg/kg) treated mice). GO enrichment analysis of spatially resolved tumor cells showed increased fatty acid and lipid metabolism in both Acly KO and EVT0185-treated mice Spatial analysis also revealed a selective increase in B cells, but not T cells, macrophages, or NKT cells, in tumors from Acly KO and EVT0185-treated mice.
from sddb import Catalog
cohort = Catalog().collection("geo-gse297081")
cohort.members # the 4 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/") Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse297081")
coll.ordered_artifacts.to_dataframe() # the 4 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()] # sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse297081 --dest data/ Licenses: 4 CC BY 4.0
Cite this collection
doi.org/10.1038/s41586-025-09297-0 ↗@article{Gautam_2025,
title = {ACLY inhibition promotes tumour immunity and suppresses liver cancer},
volume = {645},
ISSN = {1476-4687},
url = {http://dx.doi.org/10.1038/s41586-025-09297-0},
DOI = {10.1038/s41586-025-09297-0},
number = {8080},
journal = {Nature},
publisher = {Springer Science and Business Media LLC},
author = {Gautam, Jaya and Wu, Jianhan and Lally, James S. V. and McNicol, Jamie D. and Fayyazi, Russta and Ahmadi, Elham and Oniciu, Daniela Carmen and Heaton, Spencer and Newton, Roger S. and Rehal, Sonia and Bhattacharya, Dipankar and Di Pastena, Fiorella and Nguyen, Binh and Valvano, Celina M. and Townsend, Logan K. and Banskota, Suhrid and Batchuluun, Battsetseg and Jabile, Maria Joy Therese and Payne, Alice and Lu, Junfeng and Desjardins, Eric M. and Kubota, Naoto and Tsakiridis, Evangelia E. and Mistry, Bejal and Aganostopoulos, Alex and Houde, Vanessa and Dansercoer, Ann and Verschueren, Koen H. G. and Savvides, Savvas N. and Hammill, Joanne A. and Bezverbnaya, Ksenia and Muti, Paola and Tsakiridis, Theodoros and Dai, Wenting and Jiang, Lei and Hoshida, Yujin and Larché, Mark and Bramson, Jonathan L. and Friedman, Scott L. and Verstraete, Kenneth and Wang, Dongdong and Steinberg, Gregory R.},
year = {2025},
month = July,
pages = {507–517}
}