Jagged1 Tregs mediate lymphatic remodeling in tumor-draining lymph nodes.

Publication date: Jul 06, 2026

Tumor-draining lymph nodes (tdLNs) undergo extensive stromal remodeling during tumor progression, but the immune signals that shape this process remain unclear. Here, using the B16-F10 melanoma model, we examine the role of Jagged1-expressing regulatory T cells (Jag1 Tregs) in tdLN remodeling. Jag1 expression is increased in late-stage versus early-stage tdLN Tregs. Conditional deletion of Jag1 in Tregs (Foxp3) attenuates tdLN expansion without altering effector T cell abundance or activation. Bulk transcriptomic analysis identifies stromal-related transcriptional changes in Foxp3 tdLNs, including altered expression of genes linked to lymphatic endothelial cell (LEC) biology. Consistent with this, flow cytometry and histological analysis show reduced tdLN lymphatic expansion, while fluorescein isothiocyanate (FITC)-dextran tracing indicates altered lymphatic drainage. Jag1 Tregs are also detected in tdLNs in patients with melanoma. Together, these findings identify Jag1 Tregs as regulators of the tdLN lymphatic microenvironment during melanoma progression.

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Concepts Keywords
Biology CP: cancer
F10 CP: immunology
Late Jag1
Remodeling Jagged1
Tumor lymphangiogenesis
lymphatic drainage
lymphatic endothelial cells
melanoma
Notch signalling
Regulatory T cells
Tregs
tumour-draining lymph nodes

Semantics

Type Source Name
disease MESH tumor
disease MESH melanoma
pathway KEGG Melanoma
drug DRUGBANK Fluorescein
drug DRUGBANK Dextran

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