Tumor Immune Microenvironment Modification by Nanosecond Electric Pulses

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Nanosecond electric pulse (nsEP) technology has been utilized to successfully treat many types of tumors in animal models. The safety of nsEP treatment for skin basal cell carcinoma has been reported in clinical trial. Importantly, we have demonstrated that in addition to local ablation, nsEP treatment results in favorable immune outcomes including potent immune protection and/or strong systemic effects in mouse pancreatic and orthotopic breast and rat hepatocellular carcinoma models. Nevertheless, how nsEP treatment induces such a strong immune protection in the tumor microenvironment predominating with immunosuppression is not fully understood.

Mouse 4T1 breast cancer, which has demonstrated immunosuppressive dominance in the literature, was utilized to characterize changes of immune cell dynamics, cell death, function, and metabolism in the tumor microenvironment. We have discovered that nsEP treatment: (1) Collapses immunosuppression by selective eradication of regulatory T cells (Tregs) and tumor-associated macrophages (TAMs); (2) Reprograms metabolism for immune cells activation and differentiation; (3) Promotes TAM-M1 polarization; (4) Impairs the function of immunosuppressor cells; (5) induces cytotoxic T cells and tissue resident memory T cells in the tumor microenvironment. The mechanisms underlying these pro-immunostimulatory changes following nsEP treatment will be proposed and need further investigations.


0000-0002-7280-7888 (Guo), 0000-0003-0853-8641 (Nanajian), 0000-0002-0672-2202 (Ruedlinger),0000-0002-6075-9452 (Beebe)

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