瘤内皮通过脂肪酸递送的增加促进了转移性外生长
Deanna N Edwards1,2, Shan Wang1, Kelby Kane3
1Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
JCI insight
|April 8, 2025
概括
瘤血管为转移性瘤提供脂肪酸 (FA),促进生长和免疫抑制. 通过内皮mTORC1抑制阻断这种营养供应,可以减少转移并增强抗瘤免疫力.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 转移需要脂肪酸 (FA) 等营养物质,以促进瘤生长和免疫规避.
- 调节向转移部位的FA供应的机制仍然不清楚.
- 瘤微环境 (TME) 免疫抑制对于转移性生长至关重要.
研究的目的:
- 为了研究瘤内皮如何调节脂肪酸供应到转移性的.
- 确定mTORC1信号在内皮脂肪酸运输中的作用.
- 探索针对转移性癌症内皮细胞营养递送的治疗策略.
主要方法:
- 使用内皮细胞特异性淘汰小鼠模型 (RptorECKO) 来删除Raptor,mTORC1的一个关键组件.
- 服用低剂量的恒利木斯来选择性地抑制内皮mTORC1.1.
- 评估了转移性瘤负担和T细胞介导的细胞毒性标志物.
- 通过内分泌体研究了通过内分泌体传递的超内皮脂肪酸.
主要成果:
- 内皮细胞特异性删除Raptor (RptorECKO) 显著降低了转移性瘤负担.
- 降低转移性负担与改善的T细胞细胞毒性标记物相关.
- 针对性抑制内皮mTORC1与everolimus增强免疫检查点反应.
- 确定了一种新的超内皮FA传递过程,该过程依赖于mTORC1活动.
结论:
- 瘤内皮积极向转移性中提供脂肪酸,促进瘤生长和免疫抑制.
- 内皮质mTORC1信号传递对于跨内皮质脂肪酸输送和转移性生长至关重要.
- 向内皮mTORC1代表了一种有前途的治疗策略,以增强抗瘤免疫力和控制转移性疾病.
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