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-DR^hi 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：

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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。