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

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 

机构地区：[1]Shanghai Key Laboratory of Regulatory Biology,School of Life Sciences,East China Normal University,Shanghai 200241,China [2]Prenatal Diagnosis Center,Department of Clinical Laboratory,Changning Maternity and Infant Health Hospital,East China Normal University,Shanghai 200051,China [3]Key Laboratory of Acupuncture and Immunological Effects,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [4]Fengxian Hospital Affiliated to Southern Medical University,Shanghai 201400,China [5]Shanghai Yuyao Biotech Co.,Ltd.,Shanghai 200241,China

出　　处：《Genes & Diseases》2024年第4期411-425,共15页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82073310 to Z.Yi,81830083 to M.Liu,81802970 to S.P.);the National Key R&D Program of China(No.2018YFA0507001 to M.Liu);The Science and Technology Commission of Shanghai Municipality,China(No.20JC1417900 to Z.Yi,22QB1405600 to S.P);ECNU Construction Fund of Innovation and Entrepreneurship Laboratory(Shanghai,China)(No.44400-20201-532300/021 to Z.Yi);ECNU Public Platform for innovation(Shanghai,China)(011 to S.P),and Pujiang Scholar Program Award(Shanghai,China)(No.22PJ1402700 to Y.H).

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 gastric 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 significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse model.Furthermore,adminis-tration of YYo01 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 YYo01 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 YYo01 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combination with other drugs.

关 键 词：EP4 IMMUNOMODULATION SYNERGY Tumor microenvironment YY001 

分 类 号：R730.51[医药卫生—肿瘤]