2. Academic Validation
  3. Microbiota-derived urocanic acid triggered by tyrosine kinase inhibitors potentiates cancer immunotherapy efficacy

Microbiota-derived urocanic acid triggered by tyrosine kinase inhibitors potentiates cancer immunotherapy efficacy

  • Cell Host Microbe. 2025 Jun 11;33(6):915-931.e9. doi: 10.1016/j.chom.2025.04.022.
Mengying Zhang 1,  Zhonghong Wei 2,  Bin Wei 3,  Changjie Lai 1,  Gangfan Zong 2,  Enxiang Tao 1,  Minmin Fan 4,  Yehua Pan 2,  Bingyan Zhou 1,  Luping Shen 1,  Jingjing Wu 3,  Qingqing Wang 1,  Ying Peng 1,  Le Zhen 1,  Yunhao Wu 5,  Yin Lu 6,  Guangji Wang 7,  Fang Zhou 8,  Yunlong Shan 9
Affiliations

Affiliations

  • 1 Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Jiangsu Key Laboratory for Pharmacology and Safety Research of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 3 Department of Oncology, the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.
  • 4 The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 5 Shandong Provincial Hospital, Medical Science and Technology Innovation Center, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China.
  • 6 Jiangsu Key Laboratory for Pharmacology and Safety Research of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: luyingreen@126.com.
  • 7 Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: guangjiwang@hotmail.com.
  • 8 Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zf1113@163.com.
  • 9 Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: immunometabolism@163.com.
PMID: 40441145 DOI: 10.1016/j.chom.2025.04.022
Abstract

Interactions between the host and the gut microbiota influence Cancer progression and treatment responses. While the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockade (ICB) has improved outcomes, some Cancer patients still have poor responses. The underlying mediators of this heterogeneity remain unclear. Here, we demonstrate that TKIs potentiate the immunotherapy response by increasing the abundance of Muribaculum and its metabolite, urocanic acid (UCA), which reduces myeloid-derived suppressor cell (MDSC) recruitment via the CXCL1-CXCR2 axis by inhibiting p65 in tumor vascular endothelial cells. Mechanistically, UCA selectively binds to the aspartic acid 31 residue of IκBα and suppresses its phosphorylation at serine 32. Compared with non-responders, clinical ICB responders present a higher UCA concentration and a greater level of Muribaculum gordoncarteri in feces, indicating both as potential predictive biomarkers for treatment response. Collectively, our findings reveal and highlight the important role of the gut microbial metabolite UCA in response to ICB.

Keywords

Muribaculum; gut microbiota; immune checkpoint blockade; tyrosine kinase inhibitors; urocanic acid.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z