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Updated: May 13, 2026

Blocking Lymph Flow by Suturing Afferent Lymphatic Vessels in Mice
Published on: May 14, 2020
Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12
Qidong Xia1,2, Jiayao Pan1,2, Xiaoqi Weng1,2
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Abstract:
High endothelial venules (HEVs) provide another portal for tumour metastasis. However, whether HEVs and other blood vessels exert different effects on tumour escape remains unknown. Here we show that tumour involvement in HEVs is an independent prognostic marker for patients with lymph node (LN)-positive female breast cancer. Tumour cells that spread via HEVs are less immunogenic and more capable of establishing distant metastases than those that spread through non-HEV blood vessels. Mechanistically, the expression of arachidonate 12-lipoxygenase (ALOX12) in HEVs is promoted by tumour-derived semaphorin 3 C (SEMA3C). Reciprocally, ALOX12-derived metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) promotes ADAR1 p150-dsRNA phase separation in tumour cells by selectively binding to ADAR1 p150. Consequently, the immune recognition of dsRNA is reduced because of the increased adenosine-to-inosine (A-to-I) RNA editing in tumour cells. Collectively, our data indicate that a unique lymphatic anatomical structure mediates specific immune evasion of migrating tumour cells.
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