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High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy
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High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy
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Journal Article
High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy
2018
Overview
Among many populations of blood cells, high dimensional analysis using mass cytometry reveals classical monocyte frequency as strong predictors of response to PD-1 blockade therapy of melanoma.
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.
