Nano‐pulse stimulation induces potent immune responses, eradicating local breast cancer while reducing distant metastases

Abstract

Nano-pulse stimulation (NPS) as a developing technology has been studied for minimally invasive, nonthermal local cancer elimination for more than a decade. Here we show that a single NPS treatment results in complete regression of the poorly immunogenic, metastatic 4T1-Luc mouse mammary carcinoma. Impressively, spontaneous distant organ metastases were largely prevented, even in those animals with incomplete tumor regression. All tumor-free mice were protected from secondary tumor cell challenge, demonstrating a vaccine-like effect. NPS treatment induced antitumor immunity, long-term memory T cells, destruction of tumor microenvironment and reversal of the massive increase of immune suppressor cells in the tumor microenvironment and blood. NPS-treated 4T1 cells exhibited release of damage-associated molecular patterns (DAMPs), including calreticulin, HMGB1 and ATP, and activated dendritic cells. Those findings suggest that NPS is a potent immunogenic cell death inducer that elicits antitumor immunity to prevent distant metastases in addition to local tumor eradication.

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

“…Open access the ubiquitin-specific peptidase inhibitor spautin-1, the antibiotic bleomycin, the protein phosphatase-2A inhibitor LB-100, the Chinese herbal medicine component shikonin and capsaicin [34][35][36][37][38] and (8) numerous physical interventions, encompassing various forms of ionizing radiation, extracorporeal photochemotherapy, hypericinbased photodynamic therapy (PDT), near-infrared photoimmunotherapy, high hydrostatic pressure, severe cytotoxic heat shock, nanopulse stimulation and electrohyperthermia. [39][40][41][42][43][44][45][46][47][48][49] Importantly, dose and administration schedules have a major impact on the ability of many of these agents to initiate productive ICD. [50][51][52] The aforementioned ICD inducers have been instrumental not only for identifying the molecular machinery that underlies the immunogenicity of some variants of RCD, 5 but also for elucidating the pathophysiological and therapeutic implications of the process.…”

Immunogenic cell death in cancer therapy: Present and emerging inducers

“…Further, the secretion of HMGB1 and ATP is observed after NPS treatment . In fact, NPS, which may be responsible for releasing DAMPs through ICD and triggering DC antigen presentation, can eliminate high percentages of primary 4T1 tumours (75‐100%) by inducing the immune response and activating adaptive immune memory . Thus, NPS is defined as a physical method that induces ER stress‐dependent ICD and its unique clinical utility is worthy of further in‐depth research.…”

From the basic science of biological effects of ultrashort electrical pulses to medical therapies

“…This is shown in Figure . More recently, nsPEF treatment of mouse breast cancer tumors has demonstrated complete ablation and the first direct evidence for nsPEF‐induced immune responses by specifically defining several immune mechanisms [Guo et al, ]. NsPEFs eliminate suppressive immune cells within the tumor and blood that prevent the immune response, induce a potent memory T cell response that attacks the tumor, and reduce distant metastasis and eradicate second untreated tumors (abscopal effect).…”