GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
| Autor: | Bianca Calì, Andrielly H. R. Agnellini, Chiara Cioccarelli, Ricardo Sanchez-Rodriguez, Andrea Predonzani, Giulia Ilaria Toffolo, Antonella Viola, Vincenzo Bronte, Giorgio Arrigoni, Francesco Zonta, Laura Albertoni, Claudia Mescoli, Ilaria Marigo, Barbara Molon |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Myeloid
Colorectal cancer T cell Immunology Biology Immunomodulation Mice Immune system Immunity Cell Line Tumor Neoplasms medicine Immunology and Allergy Animals tumor microenvironment Original Research Tumor microenvironment immunosuppression Myeloid-Derived Suppressor Cells Cancer Granulocyte-Macrophage Colony-Stimulating Factor Cell Differentiation RC581-607 medicine.disease cytokines post-translational modification reactive nitrogen species Disease Models Animal medicine.anatomical_structure Tumor progression Cancer research Disease Susceptibility Immunologic diseases. Allergy Protein Processing Post-Translational Biomarkers Signal Transduction |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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