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

Int J Cancer. 2018 Feb 1;142(3):629-640. doi: 10.1002/ijc.31071. Epub 2017 Oct 12.

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.

Keywords: breast cancer; dendritic cell activation; immune response; immunogenic cell death; nano-pulse stimulation; tumor ablation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Electric Stimulation Therapy / methods*
  • Female
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis