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Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation

Neutrophil extracellular traps (NETs) are web-like chromatin structures composed by dsDNA and histones, decorated with antimicrobial proteins. Their interaction with dendritic cells (DCs) allows DC activation and maturation toward presentation of NET-associated antigens. Differently from other types...

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Autores principales: Tripodo, Claudio, Bassani, Barbara, Jachetti, Elena, Cancila, Valeria, Chiodoni, Claudia, Portararo, Paola, Botti, Laura, Valenti, Cesare, Perrone, Milena, Ponzoni, Maurilio, Comoli, Patrizia, Lecchi, Mara, Verderio, Paolo, Curti, Antonio, Colombo, Mario P, Sangaletti, Sabina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068207/
https://www.ncbi.nlm.nih.gov/pubmed/35471185
http://dx.doi.org/10.7554/eLife.69257
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author Tripodo, Claudio
Bassani, Barbara
Jachetti, Elena
Cancila, Valeria
Chiodoni, Claudia
Portararo, Paola
Botti, Laura
Valenti, Cesare
Perrone, Milena
Ponzoni, Maurilio
Comoli, Patrizia
Lecchi, Mara
Verderio, Paolo
Curti, Antonio
Colombo, Mario P
Sangaletti, Sabina
author_facet Tripodo, Claudio
Bassani, Barbara
Jachetti, Elena
Cancila, Valeria
Chiodoni, Claudia
Portararo, Paola
Botti, Laura
Valenti, Cesare
Perrone, Milena
Ponzoni, Maurilio
Comoli, Patrizia
Lecchi, Mara
Verderio, Paolo
Curti, Antonio
Colombo, Mario P
Sangaletti, Sabina
author_sort Tripodo, Claudio
collection PubMed
description Neutrophil extracellular traps (NETs) are web-like chromatin structures composed by dsDNA and histones, decorated with antimicrobial proteins. Their interaction with dendritic cells (DCs) allows DC activation and maturation toward presentation of NET-associated antigens. Differently from other types of cell death that imply protein denaturation, NETosis preserves the proteins localized onto the DNA threads for proper enzymatic activity and conformational status, including immunogenic epitopes. Besides neutrophils, leukemic cells can release extracellular traps displaying leukemia-associated antigens, prototypically mutant nucleophosmin (NPMc+) that upon mutation translocates from nucleolus to the cytoplasm localizing onto NET threads. We tested NPMc+ immunogenicity through a NET/DC vaccine to treat NPMc-driven myeloproliferation in transgenic and transplantable models. Vaccination with DC loaded with NPMc+ NET (NPMc+ NET/DC) reduced myeloproliferation in transgenic mice, favoring the development of antibodies to mutant NPMc and the induction of a CD8(+) T-cell response. The efficacy of this vaccine was also tested in mixed NPMc/WT bone marrow (BM) chimeras in a competitive BM transplantation setting, where the NPMc+ NET/DC vaccination impaired the expansion of NPMc+ in favor of WT myeloid compartment. NPMc+ NET/DC vaccination also achieved control of an aggressive leukemia transduced with mutant NPMc, effectively inducing an antileukemia CD8 T-cell memory response.
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spelling pubmed-90682072022-05-05 Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation Tripodo, Claudio Bassani, Barbara Jachetti, Elena Cancila, Valeria Chiodoni, Claudia Portararo, Paola Botti, Laura Valenti, Cesare Perrone, Milena Ponzoni, Maurilio Comoli, Patrizia Lecchi, Mara Verderio, Paolo Curti, Antonio Colombo, Mario P Sangaletti, Sabina eLife Immunology and Inflammation Neutrophil extracellular traps (NETs) are web-like chromatin structures composed by dsDNA and histones, decorated with antimicrobial proteins. Their interaction with dendritic cells (DCs) allows DC activation and maturation toward presentation of NET-associated antigens. Differently from other types of cell death that imply protein denaturation, NETosis preserves the proteins localized onto the DNA threads for proper enzymatic activity and conformational status, including immunogenic epitopes. Besides neutrophils, leukemic cells can release extracellular traps displaying leukemia-associated antigens, prototypically mutant nucleophosmin (NPMc+) that upon mutation translocates from nucleolus to the cytoplasm localizing onto NET threads. We tested NPMc+ immunogenicity through a NET/DC vaccine to treat NPMc-driven myeloproliferation in transgenic and transplantable models. Vaccination with DC loaded with NPMc+ NET (NPMc+ NET/DC) reduced myeloproliferation in transgenic mice, favoring the development of antibodies to mutant NPMc and the induction of a CD8(+) T-cell response. The efficacy of this vaccine was also tested in mixed NPMc/WT bone marrow (BM) chimeras in a competitive BM transplantation setting, where the NPMc+ NET/DC vaccination impaired the expansion of NPMc+ in favor of WT myeloid compartment. NPMc+ NET/DC vaccination also achieved control of an aggressive leukemia transduced with mutant NPMc, effectively inducing an antileukemia CD8 T-cell memory response. eLife Sciences Publications, Ltd 2022-04-26 /pmc/articles/PMC9068207/ /pubmed/35471185 http://dx.doi.org/10.7554/eLife.69257 Text en © 2022, Tripodo et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Tripodo, Claudio
Bassani, Barbara
Jachetti, Elena
Cancila, Valeria
Chiodoni, Claudia
Portararo, Paola
Botti, Laura
Valenti, Cesare
Perrone, Milena
Ponzoni, Maurilio
Comoli, Patrizia
Lecchi, Mara
Verderio, Paolo
Curti, Antonio
Colombo, Mario P
Sangaletti, Sabina
Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation
title Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation
title_full Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation
title_fullStr Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation
title_full_unstemmed Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation
title_short Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation
title_sort neutrophil extracellular traps arm dc vaccination against npm-mutant myeloproliferation
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068207/
https://www.ncbi.nlm.nih.gov/pubmed/35471185
http://dx.doi.org/10.7554/eLife.69257
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