维斯塔免疫检查点使辐射疗法诱导的抗瘤免疫反应变得模糊
Dhanya K Nambiar1, Sainiteesh Maddineni2, Jimpi Langthasa1
1Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Cell reports
|June 28, 2025
概括
癌症的放射治疗可能由于免疫抑制性髓状细胞而失败. 在这些细胞上准V-域免疫球蛋白抑制T细胞激活 (VISTA) 增强了癌症治疗期间的瘤控制和免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 放射治疗研究 放射治疗研究
背景情况:
- 放射治疗 (RT) 对于治疗像头癌 (HNC) 这样的固体瘤至关重要.
- 矛盾的是,RT可以促进免疫抑制性髓状细胞,导致治疗耐药性.
- 在RT期间,V-域免疫球蛋白抑制T细胞激活 (VISTA) 在髓状细胞中的作用尚不清楚.
研究的目的:
- 在HNC的RT背景下,研究VISTA对髓状细胞的功能.
- 评估针对各种临床前癌症模型的VISTA结合RT的治疗潜力.
主要方法:
- 对小鼠和人类HNC瘤微环境 (TME) 的髓状细胞VISTA表达的分析.
- 在接受RT治疗的VISTA淘汰赛 (VISTA-/-) 小鼠中评估瘤控制和免疫反应.
- 在临床前癌症模型 (HNC,乳腺,结肠直肠) 中使用抗VISTA抗体和RT组合治疗的评估.
- 单细胞RNA测序 (sc-RNA-seq) 用于分析髓状细胞的特性.
主要成果:
- 在HNC TME的髓状细胞上观察到高VISTA表达,随着RT增加.
- VISTA-/-小鼠通过RT增强了瘤控制,其特征是抗瘤起源的髓状细胞.
- 在多个模型中,抗VISTA抗体和RT的联合治疗显著降低了瘤体积.
- 联合治疗通过骨髓层再极化增强了全身抗瘤免疫力和瘤内T细胞功能.
结论:
- 骨髓细胞上的VISTA在固体瘤中对RT耐药性起着至关重要的作用.
- 针对VISTA是一个有希望的策略,可以克服RT诱导的免疫抑制.
- 将抗VISTA治疗与RT结合起来,可以显著提高治疗疗效和抗瘤免疫反应.
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