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

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number718098
Pages (from-to)1-13
Number of pages13
JournalFront. Immunol.
Publication statusPublished - Oct 5 2021


  • Animals
  • Biomarkers
  • Cell Differentiation
  • Cell Line, Tumor
  • Cytokines/metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
  • Immunomodulation
  • Mice
  • Myeloid-Derived Suppressor Cells/immunology
  • Neoplasms/etiology
  • Protein Processing, Post-Translational
  • Reactive Nitrogen Species/metabolism
  • Signal Transduction
  • Tumor Microenvironment/immunology


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