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0This research identifies high endothelial venules (HEVs) in lymph nodes as critical drivers of immune evasion for migrating breast cancer cells. By utilizing deep learning algorithms and mouse models, the study reveals that tumor cells spreading through HEVs are more lethal and less visible to the immune system than those traveling via other blood vessels. This process is triggered by the tumor-derived protein SEMA3C, which induces HEVs to produce the metabolite 12-HETE. This signaling molecule promotes liquid-liquid phase separation of the enzyme ADAR1 p150, enhancing RNA editing that shields cancer cells from being detected by innate immune sensors. Consequently, these findings highlight the ALOX12-12-HETE pathway as a promising therapeutic target to prevent metastatic escape.
References:
Xia Q, Pan J, Weng X, et al. Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12[J]. Nature Communications, 2026.
