Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

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外文摘要：Gastric cancer is highly prevalent among digestive tract tumors.Due to the intri-cate nature of the gastric cancer immune microenvironment,there is currently no effective treatment available for advanced gastnc cancer.However,there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4(EP4)in gastric cancer.In our previous study,we identified a novel small molecule EP4 receptor antagonist called YY001.Treatment with YY001 alone demonstrated a signihcant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse model.Furthermore,adminis-tration of YY001 stimulated a robust immune response within the tumor microenvironment,characterized by increased infiltration of antigen-presenting cells,T cells,and M1 macro-phages.Additionally,our research revealed that YY001 exhibited remarkable synergistic ef-fects when combined with the PD-1 antibody and the clinically targeted drug apatinib,rather than fluorouracil.These findings suggest that YY001 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combi-nation with other drugs.

外文关键词：

EP4ImmunomodulationSynergyTumor microenvironmentYY001

作者：

Mengmeng Guo、Pan Hu、Jiayi Xie、Kefu Tang、Shixiu Hu、Jialiang Sun、Yundong He、Jing Li、Weiqiang Lu、Huirong Liu、Mingyao Liu、Zhengfang Yi、Shihong Peng

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作者单位：

Shanghai Key Laboratory of Regulatory Biology,School of Life Sciences,East China Normal University,Shanghai 200241,China

Prenatal Diagnosis Center,Department of Clinical Laboratory,Changning Maternity and Infant Health Hospital,East China Normal University,Shanghai 200051,China

Key Laboratory of Acupuncture and Immunological Effects,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China

Fengxian Hospital Affiliated to Southern Medical University,Shanghai 201400,China

Shanghai Yuyao Biotech Co.,Ltd.,Shanghai 200241,China

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基金：

国家自然科学基金国家自然科学基金国家自然科学基金国家重点研发计划上海市科委项目上海市科委项目ECNU Construction Fund of Innovation and Entrepreneurship Laboratory(Shanghai,China)ECNU Public Platform for innovation(Shanghai,China)Pujiang Scholar Program Award(Shanghai,China)

项目编号：

8207331081830083818029702018YFA0507001 to M.Liu20JC141790022QB140560044400-20201-532300/02101122PJ1402700

出版年：

2024

DOI：

10.1016/j.gendis.2023.101164

基因与疾病(英文)

ISSN：

年,卷(期)：2024.11(4)