Weitiao No.3(微调3号方)enhances the efficacy of anti-programmed cell death protein-1 immunotherapy by modulating the intestinal microbiota in an orthotopic model of gastric cancer mice  

作　　者：HUANG Xiaona LI Yuzhen ZHU Chenyang ZHU Hengzhou JIANG Chenyu ZHU Xiaodan ZHANG Chencen JIN Chunhui 

机构地区：[1]Department of Oncology,Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine(Wuxi Hospital of Traditional Chinese Medicine),Wuxi 214071,China

出　　处：《Journal of Traditional Chinese Medicine》2024年第5期906-915,共10页中医杂志（英文版）

基　　金：the National Natural Science Foundation of China:to Explore the Role and Mechanism of Weitiao No.3 in Promoting Immunotherapy of Gastric Cancer by Activating Peroxisome Proliferator-activated Receptor-γ/AMP-activated Protein Kinase Signaling Pathway through Short Chain Fatty Acid based on Intestinal Flora(No.82274269);the Nature Foundation of Nanjing University of Chinese Medicine:to Investigate the Effect and Mechanism of Weitiao No.3 on Immunotherapy of Gastric Cancer based on Peroxisome Proliferator-activated Receptor-γ/AMP-activated Protein Kinase Signaling Pathway(No.XZR2020079);the Wuxi Administration of Traditional Chinese Medicine Scientific Research Project:Clinical and Basic Study on the Effect of Weitiao No.3 Mixture on Immunotherapy of Gastric Cancer by Regulating Intestinal Microecology(No.ZYKJ201906)。

摘　　要：OBJECTIVE:To explore the effects of Weitiao No.3(微调3号方,WD-3)on anti-programmed cell death protein-1(PD-1)immunotherapy in gastric cancer(GC).METHODS:The intestinal microbiota was analyzed by 16S rDNA sequencing of fecal samples from three groups:healthy people(Health),GC patients(GC),and WD-3-treated GC patients(WD-3).Next,we established an orthotopic model of GC mice,which were treated with anti-PD-1,WD-3,or an inoculation of intestinal bacteria.Immune markers CD3,CD4,CD8,and forkhead box protein P3(FOXP3),and the cell proliferation marker Ki67,were evaluated by immunohistochemistry.Cell apoptosis in GC tumors was assessed by terminaldeoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling staining.Enzyme-linked immunosorbent assays(ELISAs)were performed to analyze the serum levels of the following cytokines in GC mice:tumor necrosis factor(TNF)-α,interleukin(IL)-2,IL-6,IL-10,interferon(IFN)-γ,and transforming growth factor(TGF)-β.RESULTS:Sequencing data showed that there were significant differences in the composition of the gut microbial community among the three human groups.The gut bacteria in the three groups mainly comprised the phyla Firmicutes,Proteobacteria,Bacteroidetes,and Actinobacteria.At the genus level,the relative abundances of Bifidobacterium and Coprococcus showed significant decreases in the GC group,and an obvious increase in the WD-3 group,compared with the Health group.Interestingly,the relative abundance of Saccharopolyspora was only detected in the WD-3 group.The results of in vivo experiments in GC mice showed that WD-3 or anti-PD-1 treatment increased the levels of CD3+,CD4+,and CD8+T cells,but decreased the levels of FOXP3+regulatory T cells.Furthermore,WD-3 or PD-1 antibody treatment inhibited proliferation and promoted apoptosis of GC tumor cells.ELISA analysis showed that WD-3 or PD-1 antibody treatment facilitated TNF-α,IL-2,and IFN-γexpression,while suppressing IL-6,IL-10,and TGF-βexpression.Combination therapy with WD-3 and anti-PD-1 intensi

关 键 词：stomach neoplasms IMMUNOTHERAPY programmed cell death 1 receptor gastrointestinal microbiome Weitiao No.3 

分 类 号：R735.2[医药卫生—肿瘤] R-332[医药卫生—临床医学]