Glut3 is a critical metabolic determinant of Treg-mediated immunosuppression in tumors (IMAGE)

Pohang University of Science & Technology (POSTECH)

Glut3 is a critical metabolic determinant of Treg-mediated immunosuppression in tumors

Caption

Glut3 is specifically expressed in tumor-infiltrating Treg cells (TIL-Tregs), where it facilitates enhanced Glucose uptake that drives uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis through the hexosamine biosynthesis pathway. Elevated UDP-GlcNAc levels promote post-translational O-linked N-acetylglucosamine modification (O-GlcNAcylation) of cellular factors. One key target of this modification is the c-Rel subunit of the NF-κB transcription factor, whose O-GlcNAcylation enhances the expression of NF-κB target genes essential for Treg-mediated immunosuppression. Loss of Glut3 in Treg cells reduces c-Rel O-GlcNAcylation, thereby diminishing immunosuppression and leading to reduced tumor growth. These results suggest that developing new drugs targeting GLUT3 or the O-GlcNAcylation pathway in Treg cells could improve outcomes for cancer patients by enhancing anti-tumor immunity within the tumor microenvironment.

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POSTECH

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