Targeting Tumor-associated CCR2+ Macrophages with Proteolipid Nanovesicles to Inhibit Pancreatic Cancer Recurrence Following Irreversible Electroporation

Irreversible electroporation (IRE) has emerged as a promising radical ablative therapy for PDAC; however, its clinical efficacy is hindered by the high recurrence rate. Herein, using a preclinical orthotopic PDAC tumor model, we comprehensively characterized the tumor immune microenvironment following IRE treatment through scRNA-seq. Our findings provide direct evidence that IRE treatment induces a CCR2+ tumor-associated macrophages (CCR2+ TAMs)-mediated immunosuppressive microenvironment in the residual tumor, ultimately accelerating tumor recurrence. Targeting CCR2+ TAMs enhances antitumor immunity and improves the chemotherapeutic response in PDAC. Overall design: Following the establishment of orthotopic pancreatic tumors in mice, tumors were treated with irreversible electroporation (IRE) or subjected to sham surgery once they reached a certain size. Three days post-treatment, tumor samples were collected and analyzed using 10x Genomics scRNA-seq analysis.