Adoptive Dendritic Cell Therapy Remodels the Tumor Microenvironment After Irreversible Electroporation and Induces Durable Antitumor Responses
Introduction: Irreversible electroporation (IRE) is a nonthermal tumor ablation technique, but its efficacy is limited by incomplete ablation and inadequate immune activation. This study investigates whether combining IRE with adoptive dendritic cell (DC) therapy can overcome these limitations.Materials and Methods: We systematically characterized tumor microenvironment (TME) remodeling after IRE using multiparameter flow cytometry, single-cell RNA sequencing, and multiplex immunohistochemistry. Bone marrow-derived DCs (BMDCs) were generated using FLT3L/GM-CSF/IL-4 and thoroughly characterized phenotypically and functionally. Therapeutic efficacy was evaluated in B16F10 ("cold") and MC38 ("hot") tumor models, with additional assessment of PD-1 blockade and tumor rechallenge experiments.Results: IRE alone activated resident CD8+ T cells but failed to achieve durable tumor control in cold tumors. Adoptive transfer of BMDCs post-IRE substantially reshaped the TME by enhancing CD4+ Th1 infiltration and neutrophil activation, resulting in significant tumor regression. The combination therapy promoted broader T cell receptor repertoire diversity and shifted antitumor mechanisms toward inflammatory killing. Triple therapy with PD-1 blockade further improved efficacy, achieving 83% complete response rate and durable antitumor immunity.Conclusions: IRE combined with adoptive DC therapy synergistically enhances antitumor immunity by remodeling the TME and represents a promising translatable strategy for solid tumors.