Disrupting EDEM3-induced M2-like macrophage trafficking by glucose restriction overcomes resistance to PD-1/PD-L1 blockade

Abstract

	•Cancer-associated fibroblasts (CAFs) can enhance PD-L1 glycosylation through the glycosyltransferase EDEM3, contributing to immune evasion during tumour progression.
	•EDEM3 predominantly activates the recruit M2-like macrophages via a glucose metabolism-dependent mechanism.
	•Blocking glucose utilization antagonizes recruiting and polarizing M2-like macrophages synergistically with PD-1 antibody to improve anticancer immunity.

Keywords

2-DG / antitumour immunity / cancer-associated fibroblasts / fasting-mimicking diet / glycosyltransferase EDEM3 / M2-like macrophage / PD-L1 glycosylation

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.