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Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance

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 transc...

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Autori principali: Haist, Maximilian (Autore) , Bärtsch, Marc-Andrea (Autore) , Reticker-Flynn, Nathan E. (Autore) , Lu, Guolan (Autore) , Kempchen, Tim N. (Autore) , Chu, Pauline (Autore) , Vazquez, Gustavo (Autore) , Chen, Han (Autore) , Sunwoo, John B. (Autore) , Zhang, Weiruo (Autore) , Laseinde, Eyiwunmi (Autore) , Adami, Bonny (Autore) , Zimmer, Stefanie (Autore) , Kaufman, Justus (Autore) , Le, Quynh Thu (Autore) , Gentles, Andrew J. (Autore) , Kong, Christina S. (Autore) , Plevritis, Sylvia K. (Autore) , Goltsev, Yury (Autore) , Hickey, John W. (Autore) , Nolan, Garry (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 9 March 2026
In: Cancer cell
Year: 2026, Volume: 44, Fascicolo: 3, Pages: 604-623
ISSN:1878-3686
DOI:10.1016/j.ccell.2026.01.003
Accesso online:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1016/j.ccell.2026.01.003
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1535610826000425
Testo
Note sull'autore:Maximilian Haist, Marc-A. Baertsch, Nathan E. Reticker-Flynn, Guolan Lu, Tim N. Kempchen, Pauline Chu, Gustavo Vazquez, Han Chen, John B. Sunwoo, Weiruo Zhang, Eyiwunmi Laseinde, Bonny Adami, Stefanie Zimmer, Justus Kaufman, Quynh Thu Le, Andrew J. Gentles, Christina S. Kong, Sylvia K. Plevritis, Yury Goltsev, John W. Hickey, and Garry P. Nolan
Descrizione
Riassunto: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.
Descrizione del documento:Online veröffentlicht am: 29. Januar 2026
Version of record: 9. März 2026
Gesehen am 25.08.2026
Descrizione fisica:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2026.01.003

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