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 TITLE=GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.718098 DOI=10.3389/fimmu.2021.718098 ISSN=1664-3224 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.