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Cryogel-Based Dendritic Cell Immunotherapy for Post-Surgical Breast Cancer Treatment
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Cryogel-Based Dendritic Cell Immunotherapy for Post-Surgical Breast Cancer Treatment

Lam-Duc-Huy Nguyen, Sheng-Liang Cheng, Yu-Ting Yen, Hsin-Mei Lee, Te-Haw Wu, Jane Wang, Shu-Yi LinYunching Chen
Advanced science, 卷.12(37), e03238
01/10/2025
PMID: 40642931

摘要

Animals Cell Line, Tumor Cryogels Dendritic Cells - immunology Doxorubicin - pharmacology Female Humans Immune Checkpoint Inhibitors - pharmacology Immunotherapy - methods Mice Triple Negative Breast Neoplasms - immunology Triple Negative Breast Neoplasms - therapy Tumor Microenvironment - immunology
Triple-negative breast cancer (TNBC) is an aggressive malignancy with high mortality and limited treatment options. While surgical resection removes the primary tumor, it often fails to prevent recurrence or metastasis, and despite the promise of immunotherapy, response to immune checkpoint blockade remains poor. Here, a cryogel-based dendritic cell (DC) immunotherapy is developed incorporating gold nanodot-lipopolysaccharide (AuLPS)-loaded DCs, doxorubicin (Dox), and PD-1 immune checkpoint blockade (aPD-1+Dox+AuLPS@DC) to enhance post-surgical antitumor immunity. The AuLPS nanoparticles (NPs) stabilize LPS assembly, optimizing Th1 adjuvant activity and improving DC immunotherapy efficacy while minimizing adverse effects. The cryogel enables the sustained, localized release of therapeutic agents at the surgical site, preserving DC viability, migration, and functionality within the tumor microenvironment. This strategy enhances DC activation and potentiates robust T-cell activation in both tumor-draining lymph nodes and tumor beds, leading to durable antitumor immunity. When administered at the post-surgical site in an orthotopic TNBC model, the aPD-1+Dox+AuLPS@DC cryogel immunotherapy significantly delays tumor recurrence, reduces distant metastasis, and prolongs survival. These findings highlight cryogel-based DC immunotherapy as a promising post-surgical therapeutic strategy to enhance responses to immune checkpoint blockade and improve outcomes in TNBC.

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https://doi.org/10.1002/advs.202503238檢視
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