Abstract 4134: The abscopal effect of combination IRE with αPD-1 treatment against PDACs

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is associated with a high capacity of metastatic dissemination, which results in a dismal 5-year relative survival rate. Irreversible electroporation (IRE) represents an innovative intervention utilizing short high-voltage electric pulses to induce cell death through either permanent membrane lysis or disruption of cellular homeostasis. Previous studies from our lab have demonstrated that the combination of IRE and immune checkpoint blockade using anti-PD-1 antibody (αPD-1) enhances the infiltration of CD8+ cytotoxic T cells, significantly prolonging survival in an orthotopic murine PDAC model. However, the impact of IRE/αPD-1 on metastatic PDAC tumors, known as the abscopal effect, remains unclear. In this investigation, we bilaterally implanted C57BL/6J mice with subcutaneous KRAS* PDAC tumors, treating the right flank tumors with or without IRE, in conjunction with or without αPD-1 administered intraperitoneally. Tumor growth in both the treated (with or without IRE) and untreated (abscopal) left flank tumors was closely monitored until humane euthanasia or long-term survival. In a separate study, mice serum and tumor tissues were collection on the 5th day post-IRE/αPD-1 treatment. Luminex cytokine assays were conducted on the collected serum, and immunostaining was performed on tumor tissue. Results demonstrated significantly enhanced antitumor activity in both IRE-treated and untreated tumors on mice treated with combined IRE and αPD-1, leading to a marked extension of overall survival. Luminex cytokine assays revealed a substantial increase in crucial cytokines, including IL-2, IFN-gamma, IL-18, IL-19, and IL-3, known for their pivotal roles in fostering cytotoxic T lymphocyte development, promoting T cell differentiation into effector T cells, and facilitating the recruitment of effector CD8+ T cells to the tumor microenvironment. Moreover, immunofluorescence staining of tumor tissue illustrated a notable accumulation of CD169+ macrophages in IRE-treated tumors compared to untreated tumors. Tumors from the combined IRE with αPD-1 group exhibited increased CD8+ T cell accumulation compared to other groups. These data suggest IRE combined with PD-1 blockade promotes robust antitumor immune, leading to systemic antitumor activity and robust abscopal effect. Citation Format: Qizhen Cao, Nicholas A. Egan, Weiyi Peng, Chun Li. The abscopal effect of combination IRE with αPD-1 treatment against PDACs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4134.