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 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.