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TRAF6 Regulates the Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Tumor-Bearing Host.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Feb 25; Vol. 12, pp. 649020. Date of Electronic Publication: 2021 Feb 25 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Myeloid-derived suppressor cells (MDSCs) are immature heterogeneous cells derived from the bone marrow and they are the major component of the tumor-induced immunosuppressive environment. Tumor necrosis factor receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase, catalyzes the polyubiquitination of target proteins. TRAF6 plays a critical role in modulating the immune system. However, whether TRAF6 is involved in the regulation of MDSCs has not been thoroughly elucidated to date. In this study, we found that the expression of TRAF6 in MDSCs derived from tumor tissue was significantly upregulated compared with that of MDSCs from spleen of tumor-bearing mice. Knockdown of TRAF6 remarkably attenuated the immunosuppressive effects of MDSCs. Mechanistically, TRAF6 might improve the immunosuppression of MDSCs by mediating K63-linked polyubiquitination and phosphorylation of signal transducer and activator of transcription 3 (STAT3). Additionally, it was discovered that the accumulation of MDSCs was abnormal in peripheral blood of lung cancer patients. TRAF6 and arginase 1 were highly expressed in MDSCs of patients with lung cancer. Taken together, our study demonstrated that TRAF6 participates in promoting the immunosuppressive function of MDSCs and provided a potential target for antitumor immunotherapy.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Song, Zhang, Tian, Ma, Yin, Xu and Wang.)
- Subjects :
- Animals
Arginase genetics
Arginase immunology
Arginase metabolism
Blotting, Western
Cell Line, Tumor
Cells, Cultured
Gene Expression immunology
Humans
Immune Tolerance genetics
Lung Neoplasms genetics
Lung Neoplasms metabolism
Male
Mice, Inbred C57BL
Myeloid-Derived Suppressor Cells metabolism
Nitric Oxide immunology
Nitric Oxide metabolism
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor immunology
STAT3 Transcription Factor metabolism
Signal Transduction immunology
TNF Receptor-Associated Factor 6 genetics
TNF Receptor-Associated Factor 6 metabolism
Mice
Immune Tolerance immunology
Lung Neoplasms immunology
Myeloid-Derived Suppressor Cells immunology
TNF Receptor-Associated Factor 6 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33717204
- Full Text :
- https://doi.org/10.3389/fimmu.2021.649020