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High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy.
Nature Medicine ( IF 58.7 ) Pub Date : 2018-Feb-01 , DOI: 10.1038/nm.4466
Carsten Krieg 1 , Malgorzata Nowicka 2, 3 , Silvia Guglietta 4 , Sabrina Schindler 5 , Felix J Hartmann 1 , Lukas M Weber 2, 3 , Reinhard Dummer 5 , Mark D Robinson 2, 3 , Mitchell P Levesque 5 , Burkhard Becher 1
Affiliation  

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.

中文翻译:

高维单细胞分析预测抗 PD-1 免疫疗法的反应。

免疫检查点封锁彻底改变了癌症治疗。特别是,已发现抑制程序性细胞死亡蛋白 1 (PD-1) 可有效治疗转移性黑色素瘤和其他癌症。尽管无进展生存期显着增加,但大部分患者并未表现出持久反应。因此,迫切需要临床反应的预测性生物标志物。在这里,我们使用高维单细胞质量流式细胞术和生物信息学管道深入表征 IV 期黑色素瘤患者在 12 周抗 PD-1 免疫治疗前后外周血中的免疫细胞亚群。在治疗期间,我们观察到 T 细胞区室对免疫治疗的明显反应。然而,在开始治疗之前,+ CD16 - HLA-DR hi单核细胞。我们在一个独立的、盲法的验证队列中通过传统的流式细胞术证实了这一点,并且我们建议 PBMC 中单核细胞的频率可以用于临床决策支持。
更新日期:2018-01-08
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