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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy
Carsten Krieg1, Malgorzata Nowicka2,3, Silvia Guglietta4
1Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Abstract:
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.
Insights
Predicting anti-PD-1 immunotherapy response in melanoma patients is crucial. High frequencies of specific monocytes (CD14+CD16-HLA-DRhi) before treatment strongly predict progression-free and overall survival in advanced melanoma.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- Immune-checkpoint inhibitors, particularly anti-programmed cell death protein 1 (PD-1) therapy, have transformed cancer treatment.
- Despite successes in metastatic melanoma, many patients lack durable responses, necessitating predictive biomarkers.
Purpose of the Study:
- To identify predictive biomarkers for anti-PD-1 immunotherapy response in stage IV melanoma patients.
- To characterize immune cell subsets in peripheral blood before and during anti-PD-1 treatment.
Main Methods:
- High-dimensional single-cell mass cytometry and bioinformatics analysis of peripheral blood immune cells.
- Conventional flow cytometry for validation in an independent cohort.
Main Results:
- While T cell responses were observed during therapy, pre-treatment frequencies of CD14+CD16-HLA-DRhi monocytes were significant predictors of progression-free and overall survival.
- Validation confirmed the predictive power of these specific monocyte populations.
Conclusions:
- The frequency of specific monocyte subsets in peripheral blood mononuclear cells (PBMCs) can serve as a predictive biomarker for anti-PD-1 immunotherapy outcomes in melanoma.
- This finding may aid in clinical decision-making for immunotherapy selection.
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