Cargando…

GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors

Reactive oxygen species, including RNS, contribute to the control of multiple immune cell functions within the tumor microenvironment (TME). Tumor-infiltrating myeloid cells (TIMs) represent the archetype of tolerogenic cells that actively contribute to dismantle effective immunity against cancer. T...

Descripción completa

Detalles Bibliográficos
Autores principales: Calì, Bianca, Agnellini, Andrielly H. R., Cioccarelli, Chiara, Sanchez-Rodriguez, Ricardo, Predonzani, Andrea, Toffolo, Giulia Ilaria, Viola, Antonella, Bronte, Vincenzo, Arrigoni, Giorgio, Zonta, Francesco, Albertoni, Laura, Mescoli, Claudia, Marigo, Ilaria, Molon, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523982/
https://www.ncbi.nlm.nih.gov/pubmed/34675917
http://dx.doi.org/10.3389/fimmu.2021.718098
_version_ 1784585411362816000
author Calì, Bianca
Agnellini, Andrielly H. R.
Cioccarelli, Chiara
Sanchez-Rodriguez, Ricardo
Predonzani, Andrea
Toffolo, Giulia Ilaria
Viola, Antonella
Bronte, Vincenzo
Arrigoni, Giorgio
Zonta, Francesco
Albertoni, Laura
Mescoli, Claudia
Marigo, Ilaria
Molon, Barbara
author_facet Calì, Bianca
Agnellini, Andrielly H. R.
Cioccarelli, Chiara
Sanchez-Rodriguez, Ricardo
Predonzani, Andrea
Toffolo, Giulia Ilaria
Viola, Antonella
Bronte, Vincenzo
Arrigoni, Giorgio
Zonta, Francesco
Albertoni, Laura
Mescoli, Claudia
Marigo, Ilaria
Molon, Barbara
author_sort Calì, Bianca
collection PubMed
description Reactive oxygen species, including RNS, contribute to the control of multiple immune cell functions within the tumor microenvironment (TME). Tumor-infiltrating myeloid cells (TIMs) represent the archetype of tolerogenic cells that actively contribute to dismantle effective immunity against cancer. TIMs inhibit T cell functions and promote tumor progression by several mechanisms including the amplification of the oxidative/nitrosative stress within the TME. In tumors, TIM expansion and differentiation is regulated by the granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by cancer and immune cells. Nevertheless, the role of GM-CSF in tumors has not yet been fully elucidated. In this study, we show that GM-CSF activity is significantly affected by RNS-triggered post-translational modifications. The nitration of a single tryptophan residue in the sequence of GM-CSF nourishes the expansion of highly immunosuppressive myeloid subsets in tumor-bearing hosts. Importantly, tumors from colorectal cancer patients express higher levels of nitrated tryptophan compared to non-neoplastic tissues. Collectively, our data identify a novel and selective target that can be exploited to remodel the TME and foster protective immunity against cancer.
format Online
Article
Text
id pubmed-8523982
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85239822021-10-20 GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors Calì, Bianca Agnellini, Andrielly H. R. Cioccarelli, Chiara Sanchez-Rodriguez, Ricardo Predonzani, Andrea Toffolo, Giulia Ilaria Viola, Antonella Bronte, Vincenzo Arrigoni, Giorgio Zonta, Francesco Albertoni, Laura Mescoli, Claudia Marigo, Ilaria Molon, Barbara Front Immunol Immunology Reactive oxygen species, including RNS, contribute to the control of multiple immune cell functions within the tumor microenvironment (TME). Tumor-infiltrating myeloid cells (TIMs) represent the archetype of tolerogenic cells that actively contribute to dismantle effective immunity against cancer. TIMs inhibit T cell functions and promote tumor progression by several mechanisms including the amplification of the oxidative/nitrosative stress within the TME. In tumors, TIM expansion and differentiation is regulated by the granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by cancer and immune cells. Nevertheless, the role of GM-CSF in tumors has not yet been fully elucidated. In this study, we show that GM-CSF activity is significantly affected by RNS-triggered post-translational modifications. The nitration of a single tryptophan residue in the sequence of GM-CSF nourishes the expansion of highly immunosuppressive myeloid subsets in tumor-bearing hosts. Importantly, tumors from colorectal cancer patients express higher levels of nitrated tryptophan compared to non-neoplastic tissues. Collectively, our data identify a novel and selective target that can be exploited to remodel the TME and foster protective immunity against cancer. Frontiers Media S.A. 2021-10-05 /pmc/articles/PMC8523982/ /pubmed/34675917 http://dx.doi.org/10.3389/fimmu.2021.718098 Text en Copyright © 2021 Calì, Agnellini, Cioccarelli, Sanchez-Rodriguez, Predonzani, Toffolo, Viola, Bronte, Arrigoni, Zonta, Albertoni, Mescoli, Marigo and Molon https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Calì, Bianca
Agnellini, Andrielly H. R.
Cioccarelli, Chiara
Sanchez-Rodriguez, Ricardo
Predonzani, Andrea
Toffolo, Giulia Ilaria
Viola, Antonella
Bronte, Vincenzo
Arrigoni, Giorgio
Zonta, Francesco
Albertoni, Laura
Mescoli, Claudia
Marigo, Ilaria
Molon, Barbara
GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
title GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
title_full GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
title_fullStr GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
title_full_unstemmed GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
title_short GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
title_sort gm-csf nitration is a new driver of myeloid suppressor cell activity in tumors
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523982/
https://www.ncbi.nlm.nih.gov/pubmed/34675917
http://dx.doi.org/10.3389/fimmu.2021.718098
work_keys_str_mv AT calibianca gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT agnelliniandriellyhr gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT cioccarellichiara gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT sanchezrodriguezricardo gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT predonzaniandrea gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT toffologiuliailaria gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT violaantonella gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT brontevincenzo gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT arrigonigiorgio gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT zontafrancesco gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT albertonilaura gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT mescoliclaudia gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT marigoilaria gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors
AT molonbarbara gmcsfnitrationisanewdriverofmyeloidsuppressorcellactivityintumors