Magnetic Thermal Ablation Combined with Temporally Coordinated CpG Immunotherapy Promotes cDC1-Dependent Immune Priming in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) imposes a major global health burden, with current ablation techniques limited by invasiveness and post-treatment recurrence. Here, size-controllable, polylactic acid/iron oxide magnetic microspheres containing 30% Fe3O4 (P@Fe30 MSs) were fabricated via shirasu porous glass membrane emulsification for transarterial magnetic thermal ablation (MTA). The optimized microspheres exhibit superior magnetothermal performance under an alternating magnetic field, effectively killing tumor cells and triggering immunogenic cell death (ICD). Mechanistically, MTA-induced tumor disruption cooperates with the TLR9 agonist CpG ODN to accelerate dendritic cell maturation and promote a tumor-TDLN immune-priming cascade, featuring CD103+ cDC1 enrichment and CCR7-associated cDC1 migration dynamics, functional CD8+ T-cell activation, and systemic memory-associated immune remodeling. Crucially, direct evaluation of CpG timelines reveals that early post-MTA CpG administration significantly outperforms delayed delivery, validating a transient post-ablation immune-priming window. Furthermore, experiments in Batf3-/- mice confirm that this systemic antitumor immunity strictly depends on a cDC1- mediated priming pathway. Finally, preclinical validation in an orthotopic rabbit VX2 liver tumor model demonstrates excellent transarterial feasibility, localized metabolic tumor suppression via 18F-FDG PET imaging, and a favorable safety profile. This work establishes a remotely activated transarterial ablation platform that coordinates with temporal innate immunotherapy to drive systemic cDC1-dependent antitumor responses.