Deficiency of GLUT1 in macrophages reprograms tumor-associated macrophages to normalize tumor vasculature and retards the progression of tumors.

Authors

Yuan Fang, Wei Zou, Ling Ning, Tianle Li, Ying Huang, Xiaoxiong Song, Mengyuan Gao, Ruiqin Jia, Mingxi Zhu, Wenshi Qiu, Kexin Liu, Aiyun Wang, Jia Li, Yin Lu, Yang Zhao

Published in

International journal of biological sciences. Volume 22. Issue 13. Pages 7127-7150. Epub Jul 30, 2026.

Abstract

Tumor-associated macrophages (TAMs), a major glucose-consuming population within the tumor microenvironment (TME), utilize glycolysis to support tumor progression. Therefore, concentrating on the glycolysis of intratumoral TAMs appears to be a promising research direction for tumor therapy. In this study, we demonstrated that the key glycolytic component named glucose transporter protein 1 (GLUT1, also known as SLC2A1) is extensively expressed in TAMs and is frequently associated with tumor progression. To dissect the functions of GLUT1 in macrophages on influencing the TME, macrophage-specific Glut1 knockout mice were generated and tumor-bearing mouse models were established. It was found that macrophage-specific deletion of Glut1 retarded the development of tumors and reshaped the tumor immune microenvironment (TIME). Loss of Glut1 in macrophages limited the secretion of multiple inflammatory mediators, including IL-6, IL-10, VEGF, and CXCL2, by virtue of the GSK3β/β-catenin/CD36 signaling axis, thereby normalizing the tumor blood vessels. To pharmacologically manipulate the expression of Glut1 in macrophages, M2-PLGA@WZB117 (poly lactic-co-glycolic acid, PLGA) was constructed accordingly. Interestingly, M2-PLGA@WZB117 resulted in significant inhibition in tumor progression, accompanied by tumor vascular normalization and a concurrent increase in the infiltration of CD8⁺ T cells. Therefore, our study provides new insights into reprogramming TAMs to exert impacts on tumor endothelium and thus regulating the TME, thereby hindering the development of tumors.

PMID:
42694977
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.

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