Macrophages (Mf) are the most abundant mononuclear phagocytes in tumor tissues and hold promise as therapeutic targets and indicators of disease progression. In this work, we mapped by single-cell analysis the distinct Mf populations infiltrating the invasive margin and normal adjacent regions of human colo-rectal liver metastasis (CLM), and we exploited this information to identify non redundant markers with clinical relevance. Different populations were enriched in the invasive margin, including early-mature, inflammatory Mf (MoMf) expressing the monocytic markers S100A12 and SERPINB2, and a more mature population (TAMs) expressing CD68, GPNMB and TREM2. TAMs were enriched in pathways of matrix degradation, angiogenesis and lipid metabolism, similarly to dysfunctional macrophages described in other tumors. Cell-cell interaction analysis with CD8+ T cells defined opposing roles of MoMf, predicted to interact via IL-15, and TAMs, engaging T cells via IL-20 and IL-10. By multiplex immunofluorescence in CLM sections, we confirmed that SERPINB2 and GPNMB are expressed by different Mf subsets, with distinct topographical distribution and opposite association with patient clinical outcome.
from sddb import Catalog
cohort = Catalog().collection("geo-gse254364")
cohort.members # the 2 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-gse254364")
coll.ordered_artifacts.to_dataframe() # the 2 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-gse254364 --dest data/Licenses: 2 NCBI GEO policy
@article{Cortese_2023,
title = {High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis},
volume = {11},
ISSN = {2326-6074},
url = {http://dx.doi.org/10.1158/2326-6066.cir-22-0462},
DOI = {10.1158/2326-6066.cir-22-0462},
number = {4},
journal = {Cancer Immunology Research},
publisher = {American Association for Cancer Research (AACR)},
author = {Cortese, Nina and Carriero, Roberta and Barbagallo, Marialuisa and Putignano, Anna Rita and Costa, Guido and Giavazzi, Fabio and Grizzi, Fabio and Pasqualini, Fabio and Peano, Clelia and Basso, Gianluca and Marchini, Sergio and Colombo, Federico Simone and Soldani, Cristiana and Franceschini, Barbara and Di Tommaso, Luca and Terracciano, Luigi and Donadon, Matteo and Torzilli, Guido and Kunderfranco, Paolo and Mantovani, Alberto and Marchesi, Federica},
year = {2023},
month = Jan,
pages = {405–420}
}