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@ARTICLE{Haist:309606,
author = {M. Haist and M.-A. Baertsch$^*$ and N. E. Reticker-Flynn
and G. Lu and T. N. Kempchen$^*$ and P. Chu and G. Vazquez
and H. Chen and J. B. Sunwoo$^*$ and W. Zhang and E.
Laseinde and B. Adami and S. Zimmer and J. Kaufman and Q. T.
Le and A. J. Gentles and C. S. Kong and S. K. Plevritis and
Y. Goltsev and J. W. Hickey and G. P. Nolan},
title = {{L}ymph node colonization induces tissue remodeling via
immunosuppressive fibroblast-myeloid cell niches supporting
metastatic tolerance.},
journal = {Cancer cell},
volume = {nn},
issn = {1535-6108},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2026-00256},
pages = {nn},
year = {2026},
note = {epub},
abstract = {Lymph node (LN) colonization in cancer is linked to poor
prognosis. Evidence suggests that LN colonization induces
systemic immunosuppression, facilitating distant metastasis.
We investigated LN-mediated immunosuppression in patients
with head-and-neck cancer using spatial proteomics, spatial
transcriptomics, and an in vivo model of melanoma LN
metastasis. Both primary tumors and paired LNs of
nodal-positive patients exhibit enhanced interferon-γ
signaling and an enrichment of immunosuppressive myeloid
cells and cancer-associated fibroblasts (CAFs). The spatial
intersection of these myeloid-CAF-enriched niches with
perifollicular T cell zones and LN follicles is linked to
enhanced T cell dysfunction and Treg activation therein,
thereby driving architectural LN remodeling. These immune
suppressive changes extend to adjacent non-tumor-involved LN
regions and nearby tumor-free LNs, but were not detected in
LNs of non-cancer patients, reflecting a systemic effect
that compromises anti-tumor immunity beyond the
tumor-involved LN. Hence, our findings establish LN
colonization as an active driver of systemic
immunosuppression, facilitating metastatic progression.},
keywords = {cancer-associated fibroblasts (Other) / head-and-neck
cancer (Other) / immunomodulation (Other) / lymph nodes
(Other) / metastasis (Other) / multiplex imaging (Other) /
spatial context (Other) / spatial transcriptomics (Other) /
tumor immune evasion (Other) / tumor microenvironment
(Other)},
cin = {A360},
ddc = {610},
cid = {I:(DE-He78)A360-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41616773},
doi = {10.1016/j.ccell.2026.01.003},
url = {https://inrepo02.dkfz.de/record/309606},
}