%0 Journal Article
%A Haist, Maximilian
%A Baertsch, Marc-A
%A Reticker-Flynn, Nathan E
%A Lu, Guolan
%A Kempchen, Tim Noah
%A Chu, Pauline
%A Vazquez, Gustavo
%A Chen, Han
%A Sunwoo, John B
%A Zhang, Weiruo
%A Laseinde, Eyiwunmi
%A Adami, Bonny
%A Zimmer, Stefanie
%A Kaufman, Justus
%A Le, Quynh Thu
%A Gentles, Andrew J
%A Kong, Christina S
%A Plevritis, Sylvia K
%A Goltsev, Yury
%A Hickey, John W
%A Nolan, Garry P
%T Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance.
%J Cancer cell
%V nn
%@ 1535-6108
%C Cambridge, Mass.
%I Cell Press
%M DKFZ-2026-00256
%P nn
%D 2026
%Z epub
%X 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.
%K cancer-associated fibroblasts (Other)
%K head-and-neck cancer (Other)
%K immunomodulation (Other)
%K lymph nodes (Other)
%K metastasis (Other)
%K multiplex imaging (Other)
%K spatial context (Other)
%K spatial transcriptomics (Other)
%K tumor immune evasion (Other)
%K tumor microenvironment (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41616773
%R 10.1016/j.ccell.2026.01.003
%U https://inrepo02.dkfz.de/record/309606