在大脑转移中异常的血管结构和功能与布罗利祖马布耐药性有关
Albert E Kim1,2, Kevin W Lou1,2, Anita Giobbie-Hurder3
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Neuro-oncology
|December 9, 2023
概括
免疫检查点抑制剂对大脑转移 (BM) 有希望. 异常的瘤血管,特别是大型血管,与耐药性有关,而平衡的血管结构可以预测对这些疗法的反应.
科学领域:
- 神经瘤学神经瘤学
- 免疫治疗是一种免疫疗法.
- 血管生物学 血管生物学
背景情况:
- 一个第二阶段试验 (NCT028865685) 评估了 pembrolizumab 对不同组织学的大脑转移 (BM).
- 该研究满足了其主要疗效终点,显示pembrolizumab在选择的BM患者中具有活性.
- 异常瘤血管系统可以调解免疫抑制,促使对其与免疫检查点抑制剂 (ICI) 在BM中的有效性关系进行调查.
研究的目的:
- 探索血管架构与大脑转移的内ICI疗效之间的联系.
- 根据血管特征识别BM中对ICI的潜在反应或抵抗机制.
主要方法:
- 使用了容器建筑成像,这是对体内瘤血管生理学的验证的定量指标.
- 分析了44名接受 pembrolizumab 治疗的患者的双回声 DSC/DCE MRI 数据.
- 测量包括瘤和周围瘤大脑血液体积/流量,血管大小,动脉/静脉主导,以及治疗前后的血管透性.
主要成果:
- 在ICI治疗后逐渐的BM显示出高度异常的血管系统与大口径血管.
- 响应ICI的BM具有更平衡的血管系统,包括小血管和大血管.
- 在响应的BM中观察到减少过少透气组织的趋势,这表明缺氧减少.
结论:
- 血管架构与ICI在脑转移中的有效性有关.
- 需要进一步研究血管架构调节剂及其对免疫活动的影响.
- 这些发现可能会为未来的大脑转移的组合治疗提供信息.
相关概念视频
The Blood-brain Barrier
47.4K
Overview
47.4K
Metastasis
5.6K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.6K
Mechanism of Angiogenesis
5.5K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.5K


