Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.

IF 4.1 Q2 IMMUNOLOGY Immunotherapy advances Pub Date : 2023-01-06 eCollection Date: 2023-01-01 DOI:10.1093/immadv/ltad001
Natalie M Edner, Elisavet Ntavli, Lina Petersone, Chun Jing Wang, Astrid Fabri, Alexandros Kogimtzis, Vitalijs Ovcinnikovs, Ellen M Ross, Frank Heuts, Yassin Elfaki, Luke P Houghton, Toby Talbot, Amna Sheri, Alexandra Pender, David Chao, Lucy S K Walker
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Abstract

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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利用外周血治疗前后的免疫分型对黑色素瘤的 PD-1 阻断反应进行分层。
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应答,而另一些患者则没有应答,病情出现进展。我们的目的是通过对 20 名晚期恶性黑色素瘤患者在使用 PD-1 阻断抗体 pembrolizumab 治疗前后的外周血样本进行免疫分型,确定 PD-1 导向疗法反应和进展的相关因素。我们的数据显示,对 PD-1 阻断剂有反应的患者在治疗后 CD8 T 细胞增殖增加,而病情进展与表达 CTLA-4 的 Treg 增加有关。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,对PD-1阻断疗法有反应的个体与没有反应的个体之间存在差异。这些差异与增殖标记物 Ki67、共价受体 CD28 以及抑制分子 2B4 和 KLRG1 的表达有关。虽然这些结果需要在更大的患者群体中进行验证,但它们表明,对外周血中相对较少的T细胞标记物进行流式细胞分析,有可能在开始治疗前对PD-1阻断治疗反应进行分层。
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