T细胞免疫疗法激活中性粒细胞以消除瘤抗原逃生变体
Daniel Hirschhorn1, Sadna Budhu1, Lukas Kraehenbuehl2
1Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, USA.
癌症免疫疗法可能会失败, 将CD4+T细胞治疗与免疫检查点阻断相结合,可以通过激活中性粒细胞有效地根除抗原损失黑色素瘤.
科学领域:
- 免疫学
- 癌症学
- 癌症研究
背景情况:
- 采用T细胞转移和其他癌症免疫疗法因瘤进化和抗原损失变异而面临挑战.
- 瘤逃生变体可以逃避免疫反应,限制向治疗的有效性.
研究的目的:
- 调查CD4+ T细胞治疗与免疫检查点阻断 (OX40协同刺激或CTLA-4阻断) 的结合是否可以克服黑色素瘤中的抗原损失.
- 阐明免疫机制,包括中性粒细胞在消除抗原逃逸变体中的作用.
主要方法:
- 在接受CD4+T细胞治疗的小鼠中使用黑色素瘤模型与OX40共同刺激或CTLA-4阻断相结合.
- 使用转录和流细胞测量分析来评估瘤中的免疫细胞群和激活状态.
- 研究了中性粒细胞和诱导性氧化合成酶 (iNOS) 在瘤根除中的作用.
主要成果:
- 结合疗法成功地根除了含有抗原逃逸变异的黑色素瘤,需要初步的T细胞识别.
- 完全根除瘤依赖于中性粒细胞,在一定程度上依赖于可诱导的氧化合成酶.
- 在接受免疫检查点阻塞治疗的小鼠瘤和人类黑色素瘤患者的活检中观察到显著的中性粒细胞激活.
结论:
- 结合免疫检查点阻断的CD4+T细胞治疗可以消除黑色素瘤中的抗原损失变体.
- 中性粒细胞在瘤抗原损失变体的破坏中发挥关键作用,与T细胞反应一起.
- 研究结果显示,T细胞与中性粒细胞在克服瘤免疫规避策略方面的协同作用.
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