Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.
Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.
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DOI：
10.1093/immadv/ltad001
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发表时间：
2023
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检查点抑制剂疗法在癌症中的疗效差异很大，一些患者表现出完全缓解，而另一些患者没有缓解并出现疾病进展。我们的目的是通过对20例晚期恶性黑色素瘤患者在PD-1阻断抗体pembrolizumab治疗前后的外周血样本进行免疫表型分析，确定PD-1导向治疗后的反应和进展的相关性。我们的数据显示，对PD-1阻断有反应的个体的特征在于治疗后CD 8 T细胞增殖增加，而进展与CTLA-4表达Treg的增加相关。值得注意的是，对治疗前T细胞亚群的无监督聚类分析显示，与未对PD-1阻断产生反应的个体相比，继续对PD-1阻断产生反应的个体存在差异。这些差异映射到增殖标记Ki 67和共刺激受体CD 28以及抑制分子2B 4和KLRG 1的表达。虽然这些结果需要在更大的患者队列中进行验证，但它们表明，对外周血中相对少量的T细胞标志物进行流式细胞术分析可能会在治疗开始前对PD-1阻断治疗反应进行分层。
Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg. Remarkably, unsupervised clustering analysis of pre-treatment T cell subsets revealed differences in individuals that went on to respond to PD-1 blockade compared to individuals that did not. These differences mapped to expression of the proliferation marker Ki67 and the costimulatory receptor CD28 as well as the inhibitory molecules 2B4 and KLRG1. While these results require validation in larger patient cohorts, they suggest that flow cytometric analysis of a relatively small number of T cell markers in peripheral blood could potentially allow stratification of PD-1 blockade treatment response prior to therapy initiation.
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影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
11.5
作者：
Kim, Kyung Hwan;Cho, Jinhyun;Shin, Eui-Cheol
通讯作者：
Shin, Eui-Cheol
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John
影响因子：
--
作者：
Edner NM;Wang CJ;Petersone L;Walker LSK
通讯作者：
Walker LSK