Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.962669
Keywords
melanoma; checkpoint inhibitors; nivolumab; tumor-associated neutrophil; neutrophil plasticity
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Funding
- CISI-Lab Project (University of Naples Federico II)
- Campania Bioscience (Regione Campania)
- MIUR-PRIN [2017M8YMR8_005]
- AIRC under MFAG [25123]
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PD-L1(+) PMN frequency emerges as a novel biomarker in stage IV BRAF wild type melanoma patients undergoing anti-PD-1 immunotherapy. This study found that neutrophils in melanoma patients displayed an activated phenotype and increased PD-L1 levels, and patients with lower PD-L1(+) PMN frequencies showed better survival outcomes.
Melanoma displays a rising incidence, and the mortality associated with metastatic form remains high. Monoclonal antibodies that block programmed death (PD-1) and PD Ligand 1 (PD-L1) network have revolutionized the history of metastatic disease. PD-L1 is expressed on several immune cells and can be also expressed on human neutrophils (PMNs). The role of peripheral blood PMNs as predictive biomarkers in anti-PD-1 therapy of melanoma is largely unknown. In this study, we aimed to determine activation status and PD-L1 expression on human neutrophils as possible novel biomarkers in stage IV melanoma patients (MPs). We found that PMNs from MPs displayed an activated phenotype and increased PD-L1 levels compared to healthy controls (HCs). Patients with lower PD-L1(+) PMN frequencies displayed better progression-free survival (PFS) and overall survival (OS) compared to patients with high PD-L1(+) PMN frequencies. Multivariate analysis showed that PD-L1(+) PMNs predicted patient outcome in BRAF wild type MP subgroup but not in BRAF mutated MPs. PD-L1(+) PMN frequency emerges as a novel biomarker in stage IV BRAF wild type MPs undergoing anti-PD-1 immunotherapy. Our findings suggest further evaluation of the role of neutrophil subsets and their mediators in melanoma patients undergoing immunotherapy.
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