GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors.
Front Immunol
; 12: 718098, 2021.
Article
em En
| MEDLINE
| ID: mdl-34675917
ABSTRACT
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.
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MEDLINE
Assunto principal:
Processamento de Proteína Pós-Traducional
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Fator Estimulador de Colônias de Granulócitos e Macrófagos
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Células Supressoras Mieloides
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Neoplasias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article