GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
Cali, Bianca1,8,9; Agnellini, Andrielly H. R.1,2; Cioccarelli, Chiara1,3; Sanchez-Rodriguez, Ricardo1,3; Predonzani, Andrea4; Toffolo, Giulia Ilaria4; Viola, Antonella1,3; Bronte, Vincenzo5; Arrigoni, Giorgio1; Zonta, Francesco6
2021-10-05
发表期刊FRONTIERS IN IMMUNOLOGY
ISSN1664-3224
卷号12
发表状态已发表
DOI10.3389/fimmu.2021.718098
摘要

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.

 

关键词reactive nitrogen species cytokines immunosuppression post-translational modification tumor microenvironment
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收录类别SCIE
语种英语
WOS研究方向Immunology
WOS类目Immunology
WOS记录号WOS:000708461300001
出版者FRONTIERS MEDIA SA
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128465
专题免疫化学研究所_特聘教授组_Michael Levitt组
通讯作者Marigo, Ilaria; Molon, Barbara
作者单位1.Univ Padua, Dept Biomed Sci, Padua, Italy;
2.Univ Padua, Oncol & Immunol Sect, Dept Surg Oncol & Gastroenterol, Padua, Italy;
3.Fdn Ist Ric Pediat Citta Speranza, Padua, Italy;
4.Veneto Inst Oncol IOV IRCCS, Padua, Italy;
5.Verona Univ Hosp, Dept Med, Verona, Italy;
6.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China;
7.Univ Padua, Surg Pathol & Cytopathol Unit, Dept Med DIMED, Dept Med, Padua, Italy;
8.Oncol Inst Southern Switzerland IOSI, Inst Oncol Res IOR, Bellinzona, Switzerland;
9.Univ Svizzera Italiana, Lugano, Switzerland
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GB/T 7714
Cali, Bianca,Agnellini, Andrielly H. R.,Cioccarelli, Chiara,et al. GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors[J]. FRONTIERS IN IMMUNOLOGY,2021,12.
APA Cali, Bianca.,Agnellini, Andrielly H. R..,Cioccarelli, Chiara.,Sanchez-Rodriguez, Ricardo.,Predonzani, Andrea.,...&Molon, Barbara.(2021).GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors.FRONTIERS IN IMMUNOLOGY,12.
MLA Cali, Bianca,et al."GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors".FRONTIERS IN IMMUNOLOGY 12(2021).
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