High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy

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.