Utidelone suppresses PDAC growth and enhances gemcitabine therapy by inducing immunogenic cell death

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 <i>in vitro</i> assays (CCK8, colony formation, apoptosis, and cell cycle) and <i>in vivo</i> 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 <i>in vitro</i> and <i>in vivo</i>. 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.