Edner Natalie M, Ntavli Elisavet, Petersone Lina, Wang Chun Jing, Fabri Astrid, Kogimtzis Alexandros, Ovcinnikovs Vitalijs, Ross Ellen M, Heuts Frank, Elfaki Yassin, Houghton Luke P, Talbot Toby, Sheri Amna, Pender Alexandra, Chao David, Walker Lucy S K
Institute of Immunity & Transplantation, University College London Division of Infection & Immunity, London, UK.
Royal Cornwall Hospitals NHS Trust, Truro, UK.
Immunother Adv. 2023 Jan 6;3(1):ltad001. doi: 10.1093/immadv/ltad001. eCollection 2023.
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.
检查点抑制剂疗法在癌症治疗中的疗效差异很大，一些患者表现出完全缓解，而另一些患者则无反应并出现疾病进展。我们旨在通过对20例晚期恶性黑色素瘤患者在使用PD-1阻断抗体帕博利珠单抗治疗前后的外周血样本进行免疫表型分析，来确定PD-1导向治疗后反应和进展的相关因素。我们的数据显示，对PD-1阻断有反应的个体的特征是治疗后CD8 T细胞增殖增加，而疾病进展与表达CTLA-4的调节性T细胞增加有关。值得注意的是，对治疗前T细胞亚群进行无监督聚类分析发现，与无反应的个体相比，对PD-1阻断有反应的个体存在差异。这些差异与增殖标志物Ki67、共刺激受体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有助于在治疗开始前对PD-1阻断治疗反应进行分层。
