Collections / Dendritic cell-mediated antigen presentation regulates tertiary lymphoid structure development in cancer.

Dendritic cell-mediated antigen presentation regulates tertiary lymphoid structure development in cancer.

Tertiary lymphoid structures (TLS) correlate with favorable responses to immunotherapy, yet the mechanisms governing their formation and maintenance in tumors remain poorly defined. Through high-resolution spatial mapping across human tumors, we identified a consistent accumulation of CCR7⁺ mature dendritic cells (DC) within TLS. To dissect their function, we developed a non-small cell lung cancer (NSCLC) model that recapitulates mature TLS formation. Using this model, we demonstrate that TLS induction requires IFNγ-driven maturation of type 1 conventional dendritic cells (cDC1), their migration to tumor-draining lymph nodes (tdLN), and the subsequent recruitment of tdLN-primed T cells into the tumor microenvironment. As tumors progress, TLS persist even in the absence of tdLN T cell egress, coinciding with impaired cDC1 migration to tdLN and their retention within intratumoral stromal hubs enriched in CCR7 ligands. Timed depletion of cDC1 or blockade of their localization to these hubs disrupts TLS maintenance. Strikingly, concomitant genetic ablation of both MHC class I and II on cDC1 abolishes the maintenance of TLS, T follicular helper (TFH) cells, germinal center formation, tumor-specific IgG production, and the differentiation of progenitor exhausted CD8⁺ T cells. These findings establish that local cDC1-mediated antigen presentation to CD8⁺ and CD4⁺ T cells is a central orchestrator of anti-tumor TLS programs and compelling targets for therapeutic intervention.

Datasets7
Size~304 MB
AssayVisium
Samplehuman · multiple
KindReplicates
Flag a data issue
PMID:42462020 ↗
Python · sddb client
from sddb import Catalog

cohort = Catalog().collection("geo-gse322553")
cohort.members        # the 7 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/")
Python · lamindb

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-gse322553")
coll.ordered_artifacts.to_dataframe()   # the 7 members, ordered

# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
Shell
# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse322553 --dest data/

Licenses: 7 NCBI GEO policy

Open in Vitessce
Visium
Human lung
GSM9554209
human lung non-small cell lung carcinoma 45.4 MB 2,894 spots bronze H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuelung
Conditionnon-small cell lung carcinoma
Size45.4 MB
Spots2,894
bronze H&E NCBI GEO policy Open in Vitessce
Visium
Human colon
GSM9554205
human colon colorectal carcinoma 61.6 MB 2,946 spots bronze H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuecolon
Conditioncolorectal carcinoma
Size61.6 MB
Spots2,946
bronze H&E NCBI GEO policy
Open in Vitessce
Visium
Human colon
GSM9554207
human colon colorectal carcinoma 57.5 MB 3,579 spots bronze H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuecolon
Conditioncolorectal carcinoma
Size57.5 MB
Spots3,579
bronze H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium
Human liver
GSM9554208
human liver hepatocellular carcinoma 39.0 MB 2,410 spots bronze H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissueliver
Conditionhepatocellular carcinoma
Size39.0 MB
Spots2,410
bronze H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium
Human lung
GSM9554210
human lung non-small cell lung carcinoma 30.8 MB 4,059 spots bronze H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuelung
Conditionnon-small cell lung carcinoma
Size30.8 MB
Spots4,059
bronze H&E NCBI GEO policy Open in Vitessce
Visium
Human colon
GSM9554204
human colon colorectal carcinoma 38.6 MB 2,340 spots bronze H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuecolon
Conditioncolorectal carcinoma
Size38.6 MB
Spots2,340
bronze H&E NCBI GEO policy
Open in Vitessce
Visium
Human colon
GSM9554206
human colon colorectal carcinoma 30.6 MB 2,599 spots bronze H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuecolon
Conditioncolorectal carcinoma
Size30.6 MB
Spots2,599
bronze H&E NCBI GEO policy Open in Vitessce

Cite this collection

No linked publication found — please cite the data source.