肿瘤相关的高内皮微静脉通过ALOX12驱动淋巴结中的门静脉特异性免疫逃逸
Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.
摘要(中文译文)
高内皮微静脉（HEV）为肿瘤转移提供了另一条途径。然而，HEV与其他血管是否对肿瘤逃逸发挥不同作用仍不清楚。本研究表明，肿瘤累及HEV是淋巴结（LN）阳性女性乳腺癌患者的独立预后标志物。经HEV播散的肿瘤细胞比经非HEV血管播散的肿瘤细胞免疫原性更低，且更能够建立远处转移。在机制上，肿瘤来源的信号素3C（SEMA3C）促进HEV中花生四烯酸12-脂氧合酶（ALOX12）的表达。反过来，ALOX12衍生的代谢产物12-羟基二十碳四烯酸（12-HETE）通过选择性结合ADAR1 p150，促进肿瘤细胞中ADAR1 p150-dsRNA的相分离。因此，由于肿瘤细胞中腺苷至肌苷（A-to-I）RNA编辑增加，dsRNA的免疫识别降低。总之，我们的数据表明，一种独特的淋巴解剖结构介导了迁移肿瘤细胞的特异性免疫逃逸。
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.
如何引用
AMA
Qidong Xia, Jiayao Pan, Xiaoqi Weng, Shunrong Li, Jiaqian Li, Shijian Song, et al. Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.. Nature communications. 2026; doi:10.1038/s41467-026-72412-w.
APA
Qidong Xia, Jiayao Pan, Xiaoqi Weng, Shunrong Li, Jiaqian Li, Shijian Song, et al (2026). Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.. Nature communications. https://doi.org/10.1038/s41467-026-72412-w
GB/T 7714
Qidong Xia, Jiayao Pan, Xiaoqi Weng, Shunrong Li, Jiaqian Li, Shijian Song, et al. Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.[J]. Nature communications, 2026 doi:10.1038/s41467-026-72412-w.
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