Frontiers in Immunology (Aug 2022)
PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab
- 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
Affiliations
- Leonardo Cristinziano
- Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy
- Leonardo Cristinziano
- Center for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Leonardo Cristinziano
- World Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, Italy
- Luca Modestino
- Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy
- Luca Modestino
- Center for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Luca Modestino
- World Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, Italy
- Mariaelena Capone
- Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
- Gabriele Madonna
- Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
- Domenico Mallardo
- Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
- Diana Giannarelli
- Clinical Trial Center, Biostatistics and Bioinformatics Unit, Scientific Direction, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
- Grazia D’Angelo
- Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
- Anne Lise Ferrara
- Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy
- Anne Lise Ferrara
- Center for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Anne Lise Ferrara
- World Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, Italy
- Anne Lise Ferrara
- Institute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, Italy
- Stefania Loffredo
- Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy
- Stefania Loffredo
- Center for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Stefania Loffredo
- World Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, Italy
- Stefania Loffredo
- Institute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, Italy
- Gilda Varricchi
- Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy
- Gilda Varricchi
- Center for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Gilda Varricchi
- World Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, Italy
- Gilda Varricchi
- Institute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, Italy
- Vito Vanella
- Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
- Lucia Festino
- Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
- Paolo Antonio Ascierto
- Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
- Maria Rosaria Galdiero
- Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy
- Maria Rosaria Galdiero
- Center for Basic and Clinical Immunology Research, Interdipartimental Center for basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Maria Rosaria Galdiero
- World Allergy Organization (WAO) Center of Excellence, University of Naples Federico II, Naples, Italy
- Maria Rosaria Galdiero
- Institute of Experimental Endocrinology and Oncology, Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), National Research Council (CNR), Naples, Italy
- DOI
- https://doi.org/10.3389/fimmu.2022.962669
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
