Abstract
BackgroundIrreversible electroporation (IRE) is a promising technique for the focal treatment of pathologic tissues, which involves placing minimally invasive electrodes within the targeted region. However, the knowledge about the therapeutic efficacy and immune reactions in response to IRE remains in its infancy.MethodsIn this work, to detect whether tumor ablation with IRE could trigger the immunologic response, we developed an osteosarcoma rat model and applied IRE directly to ablate the tumor. In the experiment, 118 SD rats were randomized into 4 groups: the control, sham operation, surgical resection, and IRE groups. Another 28 rats without tumor cell implantation served as the normal non-tumor-bearing group. We analyzed the changes in T lymphocyte subsets, sIL-2R and IL-10 levels in the peripheral blood one day before operation, as well as at 1, 3, 7,14 and 21 days after the operation. Moreover, splenocytes were assayed for IFN-γ and IL-4 production using intracellular cytokine staining one day before the operation, as well as at 7 and 21 days after operation.ResultsWe found that direct IRE completely ablated the tumor cells. A significant increase in peripheral lymphocytes, especially CD3+ and CD4+ cells, as well as an increased ratio of CD4+/CD8+ were detectable 7 days after operation in both the IRE and surgical resection groups. Compared with the surgical resection group, the IRE group exhibited a stronger cellular immune response. The sIL-2R level of the peripheral blood in the IRE group decreased with time and was significantly different from that in the surgical resection group. Moreover, ablation with IRE significantly increased the percentage of IFN-γ-positive splenocytes.ConclusionThese findings indicated that IRE could not only locally destroy the tumor but also change the status of cellular immunity in osteosarcoma-bearing rats. This provides experimental evidence for the clinical application of IRE in osteosarcoma treatment.
Highlights
As alternatives to surgical resection, minimally invasive tumor ablation therapies such as radiofrequency, laser, microwave and cryoablation have been developed for the treatment of benign or malignant tumors, and these techniques can be used to ablate undesirable tissue in a well-controlled and precise way [1,2,3]
Human treatment has revealed that Irreversible electroporation (IRE) is a feasible and safe technique that could offer some potential advantages over current thermal ablation techniques
We aimed to explore the immunologic response to tumor ablation with IRE using a subcutaneously xenotransplanted osteosarcoma model in rats and to provide experimental evidence supporting the clinical application of this technique for osteosarcoma treatment
Summary
As alternatives to surgical resection, minimally invasive tumor ablation therapies such as radiofrequency, laser, microwave and cryoablation have been developed for the treatment of benign or malignant tumors, and these techniques can be used to ablate undesirable tissue in a well-controlled and precise way [1,2,3]. Most of these therapies are based on thermal ablation techniques that destroy the tumor tissue by increasing or decreasing temperatures to induce irreversible cellular injury. The knowledge about the therapeutic efficacy and immune reactions in response to IRE remains in its infancy
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