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与抗PD-1反应相关的T细胞活化与瘤负担的比率

Alexander C Huang^1,2,3,4, Michael A Postow^5,6, Robert J Orlowski^1,2,3,4

¹Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

|April 12, 2017

概括

大多数黑色素瘤患者从PD-1阻断中受益,但持续反应很少发生. 血液分析显示,与瘤负担平衡的T细胞再生预示着PD-1治疗的临床成功.

科学领域:

免疫学
癌症学
翻译医学

背景情况:

针对编程细胞死亡1 (PD-1) 的单一疗法在黑色素瘤中表现出成功.
然而,大多数患者无法从PD-1阻断中获得持久的临床益处.
已经存在的T细胞透和PD- L1表达是已知的反应指标,但基于血液的分析仍未得到充分研究.

研究的目的:

在PD-1阻塞期间研究周围血液免疫细胞的药理学变化.
为了确定血基生物标志物,预测黑色素瘤PD-1治疗的临床反应.
了解免疫激活的临床失败背后的机制.

主要方法:

在 pembrolizumab 治疗之前和之后,对四期黑色素瘤患者的周围血液进行免疫分析.
循环中耗尽的CD8T细胞 (T_ex细胞) 的分析.
与治疗前瘤负担和临床反应的T_ex细胞复原幅度的相关性.

主要成果:

大多数患者对潘布罗利祖马布有免疫反应.
临床失效通常与T细胞再生和瘤负担之间的不平衡有关.
相对于瘤负担,循环T_ex细胞再生的程度与临床反应相关.

结论:

大多数接受PD-1阻断治疗的患者出现免疫复苏.
考虑到T细胞激活和瘤负担,平衡的免疫反应对于持久的临床益处至关重要.
针对循环T_ex细胞的定位,根据疾病负担进行校准,为PD-1阻断反应提供了潜在的治疗预测因子.

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