TY  - JOUR
AU  - Haist, Maximilian
AU  - Baertsch, Marc-A
AU  - Reticker-Flynn, Nathan E
AU  - Lu, Guolan
AU  - Kempchen, Tim Noah
AU  - Chu, Pauline
AU  - Vazquez, Gustavo
AU  - Chen, Han
AU  - Sunwoo, John B
AU  - Zhang, Weiruo
AU  - Laseinde, Eyiwunmi
AU  - Adami, Bonny
AU  - Zimmer, Stefanie
AU  - Kaufman, Justus
AU  - Le, Quynh Thu
AU  - Gentles, Andrew J
AU  - Kong, Christina S
AU  - Plevritis, Sylvia K
AU  - Goltsev, Yury
AU  - Hickey, John W
AU  - Nolan, Garry P
TI  - Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance.
JO  - Cancer cell
VL  - nn
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2026-00256
SP  - nn
PY  - 2026
N1  - epub
AB  - 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.
KW  - cancer-associated fibroblasts (Other)
KW  - head-and-neck cancer (Other)
KW  - immunomodulation (Other)
KW  - lymph nodes (Other)
KW  - metastasis (Other)
KW  - multiplex imaging (Other)
KW  - spatial context (Other)
KW  - spatial transcriptomics (Other)
KW  - tumor immune evasion (Other)
KW  - tumor microenvironment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41616773
DO  - DOI:10.1016/j.ccell.2026.01.003
UR  - https://inrepo02.dkfz.de/record/309606
ER  -