Journal Article

DKFZ-2026-00256

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance.

Haist, M. ; Baertsch, M.-A.DKFZ* ; Reticker-Flynn, N. E. ; Lu, G. ; Kempchen, T. N.DKFZ* ; Chu, P. ; Vazquez, G. ; Chen, H. ; Sunwoo, J. B.DKFZ* ; Zhang, W. ; Laseinde, E. ; Adami, B. ; Zimmer, S. ; Kaufman, J. ; Le, Q. T. ; Gentles, A. J. ; Kong, C. S. ; Plevritis, S. K. ; Goltsev, Y. ; Hickey, J. W. ; Nolan, G. P.

2026
Cell Press Cambridge, Mass.

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.

Keyword(s): cancer-associated fibroblasts ; head-and-neck cancer ; immunomodulation ; lymph nodes ; metastasis ; multiplex imaging ; spatial context ; spatial transcriptomics ; tumor immune evasion ; tumor microenvironment

Note: epub

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Contributing Institute(s):

1. KKE Mol. Hämatologie/Onkologie (A360)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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