Yan Li, Samuel S K Lam, Yonglin Gao, Emily Shore, David W Anderson, Tomas Hode, Robert C Martin
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引用次数: 0
Abstract
Background: This study aimed to evaluate the immunotherapeutic effect of irreversible electroporation (IRE) and IP-001 in pancreatic adenocarcinoma with metastasis.
Methods: Orthotopic models of pancreatic adenocarcinoma with hepatic oligometastasis were established by implantation of tumor tissues (derived from Pan02 or KPC cells) size 2 mm3 into the pancreas and left liver lobe in C57BL/6J mice. One week after implantation, the tumor-burden mice were subjected to saline control, IRE, IP-001, and IRE+IP-001. For IRE therapy (1000 V, 0.1 ms, 10 pulses administered 10 times), the pancreas tumor was treated, whereas the oligometastasis was untreated as the IRE off-target tumor. Intratumoral administration of IP-001(0.4 ml/kg) was performed.
Results: In the KPC oligometastatic model, IRE+IP-001 therapy significantly suppressed the growth of oligometastatic tumor. Flow cytometry showed significantly increased tumor-infiltrating lymphocytes (TILs) (e.g., CD8+ cytotoxic T lymphocytes) and significantly increased monocytes/macrophages in the oligometastatic tumor tissues from IRE+IP-001 treatment compared with the sham control. Significantly decreased Treg cells and tumor-associated macrophages (TAMs) also were found in the oligometastatic tumor tissues from IRE+IP-001 treatment compared with the sham control. In the Pan02 oligometastatic model, both IRE+IP-001 therapy and IRE+anti-PD-L1 immunotherapy significantly suppressed the growth of oligometastatic tumor, which was associated with the increased CD8+ cytotoxic T lymphocytes. However, increased monocytes/macrophages were found in the mice that had IRE+IP-001 therapy, but not in the mice that had IRE+anti-PD-L1 immunotherapy.
Conclusion: The study provided compelling evidence for the efficacy of IRE&IP-001 therapy in suppressing pancreatic tumors, including off-target oligometastatic lesions. The observed off-target effect underscores the importance of systemic immune activation in achieving effective tumor control.
期刊介绍:
The Annals of Surgical Oncology is the official journal of The Society of Surgical Oncology and is published for the Society by Springer. The Annals publishes original and educational manuscripts about oncology for surgeons from all specialities in academic and community settings.