Related Experiment Video
Updated: Dec 8, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as
Yago Pico de Coaña1, Maria Wolodarski1,2, Irene van der Haar Àvila1
1Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Blockade of the PD-1 receptor has revolutionized the treatment of metastatic melanoma, with significant increases in overall survival (OS) and a dramatic improvement in patient quality of life. Despite the success of this approach, the number of benefitting patients is limited and there is a need for predictive biomarkers as well as a deeper mechanistic analysis of the cellular populations involved in clinical responses. With the aim to find predictive biomarkers for PD-1 checkpoint blockade, an in-depth immune monitoring study was conducted in 36 advanced melanoma patients receiving pembrolizumab or nivolumab treatment at Karolinska University Hospital. Blood samples were collected before treatment and before administration of the second and fourth doses. Peripheral blood mononuclear cells were isolated and stained for flow cytometric analysis within 2 h of sample collection. Overall survival and progression-free survival (PFS) were inversely correlated with CD69 expression NK cells. In the myeloid compartment, high frequencies of non-classical monocytes and low frequencies of monocytic myeloid derived suppressor cells (MoMDSCs) correlated with response rates and OS. A deeper characterization of monocytic subsets showed that PD-L1 expression in MDSCs, non-classical and intermediate monocytes was significantly increased in patients with shorter PFS in addition to correlating inversely with OS. Our results suggest that cellular populations other than T cells can be critical in the outcome of PD-1 blockade treatment. Specifically, the frequencies of activated NK cells and monocytic subsets are inversely correlated with survival and clinical benefit, suggesting that their role as predictive biomarkers should be further evaluated.
Insights
Predictive biomarkers for PD-1 blockade therapy in melanoma may involve immune cells beyond T cells. Activated NK cells and specific monocytic subsets correlate with patient survival and treatment response.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- PD-1 receptor blockade has improved outcomes for metastatic melanoma patients.
- However, limited patient response necessitates predictive biomarkers and mechanistic understanding.
Purpose of the Study:
- To identify predictive biomarkers for PD-1 blockade therapy in advanced melanoma.
- To investigate the role of immune cell populations in treatment response.
Main Methods:
- Immune monitoring of 36 advanced melanoma patients receiving PD-1 inhibitors (pembrolizumab/nivolumab).
- Flow cytometry analysis of peripheral blood mononuclear cells collected at multiple time points.
- Correlation analysis of immune cell subsets with overall survival (OS) and progression-free survival (PFS).
Main Results:
- Inverse correlation between CD69 expression on NK cells and OS/PFS.
- High frequencies of non-classical monocytes and low frequencies of monocytic myeloid-derived suppressor cells (MoMDSCs) associated with better response and OS.
- Increased PD-L1 expression in MDSCs, non-classical, and intermediate monocytes correlated with shorter PFS and poorer OS.
Conclusions:
- Immune cell populations beyond T cells, including NK cells and monocytic subsets, are critical for PD-1 blockade outcomes.
- Activated NK cells and specific monocytic subsets may serve as predictive biomarkers for PD-1 therapy in melanoma.
