Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12
Year: 2026
Type: article
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.
Source: Nature Communications
Institutions: Sun Yat-sen University, Sun Yat-sen Memorial Hospital, First Affiliated Hospital of Zhengzhou University, The First Affiliated Hospital, Sun Yat-sen University, Third Affiliated Hospital of Sun Yat-sen University, Affiliated Hospital of Guizhou Medical University, Army Medical University, Southwest Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7160851340