FOXA1 is an epithelial transcription factor that is often found dysregulated in prostate cancer. Previous studies have reported both tumor-promoting and -inhibitory functions of FOXA1. However, a comprehensive analysis of FOXA1 in a physiological, immune-competent setting is still lacking. We here report a novel genetically engineered mouse model with Foxa1 KO in the Pten-null prostate epithelium for the study of FOXA1 loss within an immune-competent prostate tumor context. Here, we report Foxa1 loss induces prostate cancer lineage switch from a luminal-like to a more aggressive basal/squamous-like phenotype, which is accompanied by inflammatory and immunosuppressive cytokine signaling. Mechanistically, in addition to inducing luminal genes, we found FOXA1 directly inhibits several basal/squamous, inflammatory, and cytokine genes, such that its loss unleashes their expression. Moreover, Foxa1 loss induces a striking remodeling of the prostate tumor immune microenvironment, leading to increased immunosuppressive myeloid accumulation and dysfunctional and spatially confined T cells. Altogether, we report critical roles for FOXA1 loss in inducing basal/squamous de-differentiation and an immunosuppressive microenvironment.
from sddb import Catalog
cohort = Catalog().collection("geo-gse282724")
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-gse282724")
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-gse282724 --dest data/Licenses: 4 NCBI GEO policy
@article{Brea_2026,
title = {FOXA1 loss drives basal/squamous de-differentiation of prostate cancer and induces an immunosuppressive tumor microenvironment},
volume = {17},
ISSN = {2041-1723},
url = {http://dx.doi.org/10.1038/s41467-026-71121-8},
DOI = {10.1038/s41467-026-71121-8},
number = {1},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
author = {Brea, Lourdes and Shi, Hongshun and Keo, Viriya and Huang, Jing and Peng, Liu and Chu, Qi and Xie, Wanqing and Xie, Yinghua and Senthil, Sambhavi and Breneman, Matthew T. and Fan, Jie and Xie, Ping and Lu, Xiaodong and Degraff, David J. and Abdulkadir, Sarki A. and Yang, Ximing and Kosoff, David and Zhao, Jonathan C. and Zhang, Bin and Hu, Jian and Yu, Jindan},
year = {2026},
month = Mar
}