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

Shaoyong Peng; Minshan Wu; Qian Yan; Gaopo Xu; Yumo Xie; Guannan Tang; Jinxin Lin; Zixu Yuan; Xiaoxia Liang; Ze Yuan; Jingrong Weng; Liangliang Bai; Xiaolin Wang; Huichuan Yu; Meijin Huang; Yanxin Luo; Xiaoxia Liu

doi:10.1002/ctm2.70161

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (1) : e70161 DOI: 10.1002/ctm2.70161

RESEARCH ARTICLE

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

Shaoyong Peng ¹^,²
, Minshan Wu ¹^,²^,³^,⁴^,⁵^,⁶
, Qian Yan ²^,³^,⁴^,⁵^,⁶
, Gaopo Xu ²^,³^,⁴^,⁵^,⁶
, Yumo Xie ¹^,²^,³
, Guannan Tang ²^,³^,⁴^,⁵^,⁶
, Jinxin Lin ¹
, Zixu Yuan ¹
, Xiaoxia Liang ²^,³^,⁴^,⁵^,⁶^,⁷
, Ze Yuan ²^,³^,⁴^,⁵^,⁶
, Jingrong Weng ¹^,²^,³
, Liangliang Bai ⁸
, Xiaolin Wang ²^,³^,⁴^,⁵^,⁶
, Huichuan Yu ²^,³^,⁴^,⁵^,⁶
, Meijin Huang ¹
, Yanxin Luo ¹^,²^,³^,⁴^,^†
, Xiaoxia Liu ¹^,²^,³^,⁴^,⁵^,⁶^,^†

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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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Shaoyong Peng, Minshan Wu, Qian Yan, Gaopo Xu, Yumo Xie, Guannan Tang, Jinxin Lin, Zixu Yuan, Xiaoxia Liang, Ze Yuan, Jingrong Weng, Liangliang Bai, Xiaolin Wang, Huichuan Yu, Meijin Huang, Yanxin Luo, Xiaoxia Liu. Disrupting EDEM3-induced M2-like macrophage trafficking by glucose restriction overcomes resistance to PD-1/PD-L1 blockade. Clinical and Translational Medicine, 2025, 15(1): e70161 DOI:10.1002/ctm2.70161

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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.