PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.962669/full |
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| author | Leonardo Cristinziano Leonardo Cristinziano Leonardo Cristinziano Luca Modestino Luca Modestino Luca Modestino Mariaelena Capone Gabriele Madonna Domenico Mallardo Diana Giannarelli Grazia D’Angelo Anne Lise Ferrara Anne Lise Ferrara Anne Lise Ferrara Anne Lise Ferrara Stefania Loffredo Stefania Loffredo Stefania Loffredo Stefania Loffredo Gilda Varricchi Gilda Varricchi Gilda Varricchi Gilda Varricchi Vito Vanella Lucia Festino Paolo Antonio Ascierto Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero |
| author_facet | Leonardo Cristinziano Leonardo Cristinziano Leonardo Cristinziano Luca Modestino Luca Modestino Luca Modestino Mariaelena Capone Gabriele Madonna Domenico Mallardo Diana Giannarelli Grazia D’Angelo Anne Lise Ferrara Anne Lise Ferrara Anne Lise Ferrara Anne Lise Ferrara Stefania Loffredo Stefania Loffredo Stefania Loffredo Stefania Loffredo Gilda Varricchi Gilda Varricchi Gilda Varricchi Gilda Varricchi Vito Vanella Lucia Festino Paolo Antonio Ascierto Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero |
| author_sort | Leonardo Cristinziano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T21:22:37Z |
| format | Article |
| id | doaj.art-ecf947143c114c5d8398b7625b7914b1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T21:22:37Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ecf947143c114c5d8398b7625b7914b12022-12-22T01:33:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.962669962669PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumabLeonardo Cristinziano0Leonardo Cristinziano1Leonardo Cristinziano2Luca Modestino3Luca Modestino4Luca Modestino5Mariaelena Capone6Gabriele Madonna7Domenico Mallardo8Diana Giannarelli9Grazia D’Angelo10Anne Lise Ferrara11Anne Lise Ferrara12Anne Lise Ferrara13Anne Lise Ferrara14Stefania Loffredo15Stefania Loffredo16Stefania Loffredo17Stefania Loffredo18Gilda Varricchi19Gilda Varricchi20Gilda Varricchi21Gilda Varricchi22Vito Vanella23Lucia Festino24Paolo Antonio Ascierto25Maria Rosaria Galdiero26Maria Rosaria Galdiero27Maria Rosaria Galdiero28Maria Rosaria Galdiero29Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyWorld Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyWorld Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, ItalyMelanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, ItalyMelanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, ItalyMelanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, ItalyClinical Trial Center, Biostatistics and Bioinformatics Unit, Scientific Direction, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, ItalyMelanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, ItalyDepartment of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyWorld Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, ItalyInstitute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, ItalyDepartment of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyWorld Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, ItalyInstitute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, ItalyDepartment of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyWorld Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, ItalyInstitute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, ItalyMelanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, ItalyMelanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, ItalyMelanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, ItalyDepartment of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyWorld Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, ItalyInstitute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, ItalyMelanoma 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.962669/fullmelanomacheckpoint inhibitorsnivolumabtumor-associated neutrophilneutrophil plasticity |
| spellingShingle | Leonardo Cristinziano Leonardo Cristinziano Leonardo Cristinziano Luca Modestino Luca Modestino Luca Modestino Mariaelena Capone Gabriele Madonna Domenico Mallardo Diana Giannarelli Grazia D’Angelo Anne Lise Ferrara Anne Lise Ferrara Anne Lise Ferrara Anne Lise Ferrara Stefania Loffredo Stefania Loffredo Stefania Loffredo Stefania Loffredo Gilda Varricchi Gilda Varricchi Gilda Varricchi Gilda Varricchi Vito Vanella Lucia Festino Paolo Antonio Ascierto Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab Frontiers in Immunology melanoma checkpoint inhibitors nivolumab tumor-associated neutrophil neutrophil plasticity |
| title | PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab |
| title_full | PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab |
| title_fullStr | PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab |
| title_full_unstemmed | PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab |
| title_short | PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab |
| title_sort | pd l1 neutrophils as novel biomarkers for stage iv melanoma patients treated with nivolumab |
| topic | melanoma checkpoint inhibitors nivolumab tumor-associated neutrophil neutrophil plasticity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.962669/full |
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