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000309606 1001_ $$aHaist, Maximilian$$b0
000309606 245__ $$aLymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance.
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000309606 520__ $$aLymph 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.
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000309606 650_7 $$2Other$$acancer-associated fibroblasts
000309606 650_7 $$2Other$$ahead-and-neck cancer
000309606 650_7 $$2Other$$aimmunomodulation
000309606 650_7 $$2Other$$alymph nodes
000309606 650_7 $$2Other$$ametastasis
000309606 650_7 $$2Other$$amultiplex imaging
000309606 650_7 $$2Other$$aspatial context
000309606 650_7 $$2Other$$aspatial transcriptomics
000309606 650_7 $$2Other$$atumor immune evasion
000309606 650_7 $$2Other$$atumor microenvironment
000309606 7001_ $$0P:(DE-HGF)0$$aBaertsch, Marc-A$$b1
000309606 7001_ $$aReticker-Flynn, Nathan E$$b2
000309606 7001_ $$aLu, Guolan$$b3
000309606 7001_ $$0P:(DE-He78)4d263f43f1c0e1d474fb278e8f3c73ca$$aKempchen, Tim Noah$$b4
000309606 7001_ $$aChu, Pauline$$b5
000309606 7001_ $$aVazquez, Gustavo$$b6
000309606 7001_ $$aChen, Han$$b7
000309606 7001_ $$0P:(DE-HGF)0$$aSunwoo, John B$$b8
000309606 7001_ $$aZhang, Weiruo$$b9
000309606 7001_ $$aLaseinde, Eyiwunmi$$b10
000309606 7001_ $$aAdami, Bonny$$b11
000309606 7001_ $$aZimmer, Stefanie$$b12
000309606 7001_ $$aKaufman, Justus$$b13
000309606 7001_ $$aLe, Quynh Thu$$b14
000309606 7001_ $$aGentles, Andrew J$$b15
000309606 7001_ $$aKong, Christina S$$b16
000309606 7001_ $$aPlevritis, Sylvia K$$b17
000309606 7001_ $$aGoltsev, Yury$$b18
000309606 7001_ $$aHickey, John W$$b19
000309606 7001_ $$aNolan, Garry P$$b20
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