Glucose Restriction Overcomes Resistance to PD-1/PD-L1 Blockade in Colorectal Cancer
Author Information
Author(s): 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
Primary Institution: The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
Hypothesis
Can disrupting EDEM3-induced M2-like macrophage trafficking by glucose restriction improve the effectiveness of PD-1/PD-L1 blockade in colorectal cancer?
Conclusion
Blocking EDEM3-induced M2-like macrophage trafficking by glucose restriction is a promising strategy to enhance the effectiveness of immunotherapy in colorectal cancer.
Supporting Evidence
- CAFs enhance PD-L1 glycosylation through EDEM3, contributing to immune evasion.
- EDEM3 promotes M2-like macrophage recruitment, leading to PD-1/PD-L1 blockade resistance.
- Glucose restriction can reduce PD-L1 glycosylation and improve T cell infiltration.
- Fasting-mimicking diet combined with 2-DG enhances anti-tumor immunity.
Takeaway
This study shows that reducing glucose can help the immune system fight cancer better by stopping certain cells from blocking the immune response.
Methodology
The study used flow cytometry, Western blotting, proteomics analysis, and in vivo studies to assess the role of EDEM3 in immune escape and its molecular mechanisms.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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