免疫疗法
医学
质量细胞仪
CD14型
黑色素瘤
流式细胞术
CD16
肿瘤科
癌症研究
封锁
免疫学
PD-L1
T细胞
内科学
癌症免疫疗法
免疫系统
免疫检查点
生物
CD8型
受体
表型
CD3型
基因
生物化学
作者
Carsten Krieg,Małgorzata Nowicka,Silvia Guglietta,Sabrina A. Hogan,Felix J. Hartmann,Lukas M. Weber,Reinhard Dummer,Mark D. Robinson,Mitchell P. Levesque,Burkhard Becher
出处
期刊:Nature Medicine
[Springer Nature]
日期:2018-01-08
卷期号:24 (2): 144-153
被引量:594
摘要
Immune-checkpoint blockade has revolutionized cancer therapy. In particular, inhibition of programmed cell death protein 1 (PD-1) has been found to be effective for the treatment of metastatic melanoma and other cancers. Despite a dramatic increase in progression-free survival, a large proportion of patients do not show durable responses. Therefore, predictive biomarkers of a clinical response are urgently needed. Here we used high-dimensional single-cell mass cytometry and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets in the peripheral blood of patients with stage IV melanoma before and after 12 weeks of anti-PD-1 immunotherapy. During therapy, we observed a clear response to immunotherapy in the T cell compartment. However, before commencing therapy, a strong predictor of progression-free and overall survival in response to anti-PD-1 immunotherapy was the frequency of CD14+CD16-HLA-DRhi monocytes. We confirmed this by conventional flow cytometry in an independent, blinded validation cohort, and we propose that the frequency of monocytes in PBMCs may serve in clinical decision support.
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