Th1 cells inducing IFNγ response improves immunotherapy efficacy in gastric cancer  

作　　者：Qi Cao Ruidong Xue Ning Zhang 

机构地区：[1]Translational Cancer Research Center,Peking University First Hospital,Beijing 100034,China [2]International Cancer Institute,Peking University Health Science Center,Beijing 100191,China [3]Yunnan Baiyao Group,Kunming 650500,China

出　　处：《Chinese Journal of Cancer Research》2023年第3期299-315,共17页中国癌症研究（英文版）

基　　金：financially supported by the National Natural Science Foundation of China (No. 82030079, 82341005, 81972656 and 82173035);the National Science and Technology Major Project of China (No. 2022YFC3400 901);Sino-Russian Math Center in PKU。

摘　　要：Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness o

关 键 词：Gastric cancer IMMUNOTHERAPY Th1 cells IFNγresponse biomarkers 

分 类 号：R735.2[医药卫生—肿瘤]