Extracellular vesicles derived from mature dendritic cells loaded with cDC1-specific chemokine XCL1 combined with chemotherapy-induced ICD for the treatment of castration-resistant prostate cancer

作者：Zhongqiang Fan, Zhao Wang, Hui Zhang, Hao Zhang, Rui Zhao, Shimiao Zhu, Xiaoqiang Liu · 发表于：Cancer Immunology Immunotherapy · 年份：2025 · DOI：10.1007/s00262-025-04070-8 · 被引用次数：9 · 研究领域：Extracellular vesicles in disease、Prostate Cancer Treatment and Research、Immunotherapy and Immune Responses

Dendritic cells (DCs) derived extracellular vesicles represent a promising vehicle for the activation of adaptive immunity, demonstrating significant potential in the development of cancer nanovaccines. The aim of this study was to evaluate the antitumor efficacy of a functional DCs-derived extracellular vesicles in castration-resistant prostate cancer. A pre-modification strategy was employed to overexpress XCL1 in dendritic cells, enabling their extracellular vesicles to highly express XCL1 protein. In vitro experiments, prostate cancer-bearing mouse models, and OVA-expressing prostate cancer mouse models demonstrated that dendritic cells efficiently internalize extracellular vesicles derived from XCL1-overexpressing mature dendritic cells (DEX XCL1 ), thereby enhancing the chemotaxis, activation, and antigen-presenting capacity of cDC1 cells. When combined with the immunogenic cell death effect induced by cisplatin, this approach significantly increased the number and cytotoxic activity of CD8 + T cells, improved the tumor microenvironment, and effectively suppressed prostate cancer tumor growth. The coding sequence of XCL1 successfully inserted upstream of the PDGFR transmembrane domain and transfected into dendritic cells, enabling their extracellular vesicles to highly express XCL1 protein. Extracellular vesicles derived from XCL1-overexpressing mature dendritic cells not only exhibited high XCL1 expression, but were also enriched with chemokine receptor CCR7 and MHC I ...