通过抑制自适应性免疫抵抗,PD-1 阻塞诱导反应
Paul C Tumeh1, Christina L Harview2, Jennifer H Yearley3
11] University of California Los Angeles (UCLA), Los Angeles, California 90095, USA [2] Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA.
Nature
|November 28, 2014
概括
已经存在的CD8(+) T细胞在瘤边缘,表达PD-1/PD-L1,预测对抗PD-1癌症治疗的反应. 这种免疫抵抗机制凸显了对这些T细胞对于瘤回归的需要.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 针对编程死亡-1 (PD-1) 受体的向疗法在各种癌症中提供了显著的临床反应.
- 癌细胞可以通过PD-1连接体 (PD-L1) 上调来逃避免疫反应,从而导致适应性免疫抵抗.
研究的目的:
- 调查在侵袭性瘤边缘预测对抗PD-1疗法的响应中,先前存在的CD8 (((+) T细胞在预测抗PD-1疗法的作用.
- 阐明PD-1/PD-L1表达和T细胞受体 (TCR) 谱与治疗结果之间的关联.
主要方法:
- 在抗PD-1治疗 (pembrolizumab) 之前和期间,从46名转移性黑色素瘤患者的瘤样本上进行了定量免疫组织化学和多重免疫光学检测.
- 下一代测序用于T细胞受体 (TCR) 谱系分析.
- 多变量分析用于开发和验证预测模型.
主要成果:
- 响应的患者在治疗前在侵袭边缘和瘤内表现出更高数量的CD8 ((+),PD-1 ((+) 和PD-L1 ((+) 细胞.
- 在响应者中观察到PD-1和PD-L1表达的密切接近,以及更克隆的TCR谱.
- 内CD8(+) T细胞增殖与治疗期间瘤大小的减少相关.
- 一个基于侵入性边缘的CD8表达的预测模型被开发和验证.
结论:
- 通过PD-1/PD-L1轴调节的侵袭性瘤边缘的先前存在的CD8(+) T细胞对于抗PD-1阻塞后的瘤回归至关重要.
- 该研究确定了在黑色素瘤中对抗PD-1治疗反应的预测生物标志物.
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