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Targeting Mesothelin Enhances Personalized Neoantigen Vaccine Induced Antitumor Immune Response in Orthotopic Pancreatic Cancer Mouse Models

文献类型：期刊论文

作者Cai, Zhixiong3,4,5; Li, Zhenli3,4,5; Zhong, Wenting3,4,5; Lin, Fangzhou3,4,5; Dong, Xiuqing3,4,5; Ye, Honghao3,4,5; Guo, Yutong3,4,5; Chen, Geng3,4,5; Yu, Xiaoling3,4,5; Yu, Haijun1,2
刊名ADVANCED SCIENCE
出版日期2025-01-31
页码17
关键词apCAFs immunotherapy mesothelin neoantigen vaccine pancreatic cancer
DOI10.1002/advs.202407976
英文摘要The immunosuppressive microenvironment in pancreatic cancer, characterized by low tumor-specific T cells and excessive fibrosis, limits the effectiveness of immunotherapy. Here, three datasets and multi-immunofluorescence staining of tissue microarrays in pancreatic cancer indicate that mesothelin (MSLN) expression negatively correlates with cytotoxic T cells in tumor. Anti-MSLN antibody (alpha MSLN) treatment of pancreatic cancer in vivo can significantly increase T cell infiltration. Meanwhile, the combination of alpha MSLN and neoantigen peptide vaccine identified from pancreatic cancer cell lines is demonstrated to be more effective in inducing neoantigen-specific T cell generation and infiltration at subcutaneous and orthotopic pancreatic cancer models for enhancing antitumor efficacy. Single-cell transcriptome analysis shows that the combined treatment significantly reduces the proportion of fibroblasts, improves the infiltration of IFN-gamma+CD4+ and GZMK+CD8+ T cells, as well as reduces the interaction of antigen presentation-associated ligands and receptors between antigen-presenting Cancer-Associated Fibroblasts (apCAFs) and naive CD4+ T cells. The negative correlations between apCAFs and CD8+ T cells/IFN-gamma+CD4+ T cells are further confirmed in human pancreatic cancer tissues. Overall, this study demonstrates that targeting MSLN can improve neoantigen vaccine induced immune efficacy by reducing apCAFs to interrupt the conversion of naive CD4+ T cells to Tregs, and therefore increase the infiltration of tumor-specific T cells.
WOS关键词CELL ; SEQ ; ANTIBODY
资助项目National Natural Science Foundation of China ; China Postdoctoral Science Foundation[2023M730609] ; Scientific Foundation of Fujian Province[2023J06049] ; Scientific Foundation of Fujian Province[2022J011279] ; Major Research Projects for Young and Middle-aged Talent of Fujian Provincial Health Commission[2022ZQNZD014] ; Fuzhou Science and technology planning project[2023-R-003] ; Young and middle-aged talent research project of Fuzhou city[2022-S-rc5] ; [U22A20328] ; [82202982]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001409881000001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/315965]  
专题新药研究国家重点实验室
通讯作者Tang, Ruijing; Liu, Xiaolong
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Fuzhou Univ, Mengchao Medx Ctr, Fuzhou 350116, Peoples R China
4.Fujian Med Univ, Liver Ctr Fujian Prov, Fuzhou 350025, Peoples R China
5.Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol Key, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China
推荐引用方式
GB/T 7714		 Cai, Zhixiong,Li, Zhenli,Zhong, Wenting,et al. Targeting Mesothelin Enhances Personalized Neoantigen Vaccine Induced Antitumor Immune Response in Orthotopic Pancreatic Cancer Mouse Models[J]. ADVANCED SCIENCE,2025:17.
APA Cai, Zhixiong.,Li, Zhenli.,Zhong, Wenting.,Lin, Fangzhou.,Dong, Xiuqing.,...&Liu, Xiaolong.(2025).Targeting Mesothelin Enhances Personalized Neoantigen Vaccine Induced Antitumor Immune Response in Orthotopic Pancreatic Cancer Mouse Models.ADVANCED SCIENCE,17.
MLA Cai, Zhixiong,et al."Targeting Mesothelin Enhances Personalized Neoantigen Vaccine Induced Antitumor Immune Response in Orthotopic Pancreatic Cancer Mouse Models".ADVANCED SCIENCE (2025):17.

入库方式： OAI收割

来源：上海药物研究所

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