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Immunol."],"abstract":"<jats:p>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<jats:sup>+<\/jats:sup> PMN frequencies displayed better progression-free survival (PFS) and overall survival (OS) compared to patients with high PD-L1<jats:sup>+<\/jats:sup> PMN frequencies. Multivariate analysis showed that PD-L1<jats:sup>+<\/jats:sup> PMNs predicted patient outcome in BRAF wild type MP subgroup but not in BRAF mutated MPs. PD-L1<jats:sup>+<\/jats:sup> 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.<\/jats:p>","DOI":"10.3389\/fimmu.2022.962669","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T21:49:58Z","timestamp":1660081798000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with 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