Vaccine and abscopal effects result from in situ vaccination with nanosecond electric pulse treatment for breast cancer in mice

Abstract

Abstract An electrical engineering technology, nanosecond electric pulse (nsEP), has been studied to ablate local tumor in a non-thermal and minimally invasive manner. Recently, several groups including our lab discovered that animals with complete tumor ablation following nsEP treatment were protected from a second tumor challenge. Therefore, nsEP tumor ablation is also a novel in situ vaccination approach. Breast cancer is considered a low immunogenic tumor with only a small subset of patients responsive to immune checkpoint inhibitors. We found nsEP treatment resulted in not only a potent in situ vaccine effect in a poorly immunogenic 4T1 mouse breast cancer model but also an abscopal effect, a rejection of distant untreated tumor lesion. We further examined the impact of nsEP on cancer cell death, tumor microenvironment (TME) modification, the dynamic changes of local and systemic immune response. 4T1 cells treated with nsEP did not show apoptotic death markers but released damage-associated molecular patterns, including calreticulin, high mobility group protein B1, and ATP. In contrast to abundant immune suppressor cells in untreated breast TME, nsEP treatment led to a significant reduction of both myeloid-derived suppressor cells and regulatory T cells. Conversely, the ratio of tumor associated macrophages M1-like verse M2-like was reversed. An increase of tissue-resident memory T cells was observed in draining lymph nodes. In summary, our results suggest that nsEP is a novel non-drug immunogenic cell death inducer and in situ vaccination approach. Further elucidation of its mechanisms and the development of an in vivo nsEP delivery system suitable for patients is critical to warrant this novel technology toward a clinical trial.