Tumor-driven stromal reprogramming in the pre-metastatic lymph node

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Metastatic dissemination depends on a receptive niche, influenced by primary tumor signals.
• Lymph nodes, exposed to tumor signals via lymph, can be reprogrammed to support metastasis or immunosuppression.

Purpose of the Study:

• To characterize tumor-driven transcriptomic changes in stromal cells within the tumor-draining lymph node.

Main Methods:

• Single cell RNA sequencing was used to profile stromal cell reprogramming in lymph nodes of tumor-bearing and naive mice.

Main Results:

• Tumor signals imprinted marginal reticular cells (MRCs) and floor lymphatic endothelial cells (fLECs) in the lymph node subcapsular sinus.
• MRCs showed early desmoplastic CAF differentiation traits, fLECs activated chemoattractant pathways for cancer cell recruitment, and both populations exhibited metabolic and immune-modulating reprogramming.
• These alterations were specific to tumor-draining lymph nodes and not observed during inflammatory challenges.

Conclusions:

• Findings support the concept of pre-metastatic niche formation.
• Identified stromal cell reprogramming offers potential targets for future therapeutic strategies.