机构：[1]Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China[2]Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China[3]Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China[4]Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China[5]Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Utidelone (UTD1), a microtubule-stabilizing agent, shows antitumor effects in solid tumors but its role in pancreatic ductal adenocarcinoma (PDAC) is unclear. We assessed UTD1 alone and with gemcitabine (GEM) using in vitro assays (CCK8, colony formation, apoptosis, and cell cycle) and in vivo xenograft and immunocompetent KPC models. UTD1 suppressed cell proliferation, induced apoptosis, and caused G2/ M arrest dose-dependently. The UTD1+GEM combination enhanced antitumor efficacy in vitro and in vivo. Mechanistically, UTD1 + GEM increased immunogenic cell death (ICD) markers. In KPC models, the combination improved survival, reduced tumors, and increased CD4+/CD8+T cell infiltration and PD-L1 expression. Clinically, UTD1 + GEM demonstrated good tolerability, high disease control rates, and favorable immunophenotypic changes. These findings suggest UTD1 triggers ICD, enhancing immune recognition of tumor cells, and highlight its potential as a therapeutic strategy for PDAC.
基金：
Shanghai Pujiang Talent Program (2019PJD042 to C.L.), and the Beijing Science and Technology Innovation Medical Development Foundation (KC2021-JX-0186-107 to Q.L.; KC2021-JX-0186-73 to F.W.).
第一作者机构：[1]Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China[2]Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China[2]Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
推荐引用方式(GB/T 7714)：
Zhou Jingyi,Zhang Kangnan,Liu Chuan,et al.Utidelone suppresses PDAC growth and enhances gemcitabine therapy by inducing immunogenic cell death[J].ISCIENCE.2025,28(6):doi:10.1016/j.isci.2025.112509.
APA：
Zhou, Jingyi,Zhang, Kangnan,Liu, Chuan,Long, Jiang,Gu, Haitao...&Li, Qi.(2025).Utidelone suppresses PDAC growth and enhances gemcitabine therapy by inducing immunogenic cell death.ISCIENCE,28,(6)
MLA：
Zhou, Jingyi,et al."Utidelone suppresses PDAC growth and enhances gemcitabine therapy by inducing immunogenic cell death".ISCIENCE 28..6(2025)
