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

• Published in: International journal of cancer Vol. 142; no. 3; pp. 629 - 640
• Main Authors: Guo, Siqi, Jing, Yu, Burcus, Niculina I., Lassiter, Brittany P., Tanaz, Royena, Heller, Richard, Beebe, Stephen J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-02-2018
• Subjects: Ablation; Animal models; Animals; Antitumor activity; Apoptosis; Breast cancer; Calreticulin; Cancer; Cancer vaccines; Carcinoma; Cell death; Cell Line, Tumor; Damage patterns; dendritic cell activation; Dendritic cells; Electric pulses; Electric Stimulation Therapy - methods; Female; HMGB1 protein; Immune response; immunogenic cell death; Immunogenicity; Immunological memory; Long term memory; Lymphocytes; Lymphocytes T; Mammary gland; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - therapy; Medical research; Memory cells; Metastases; Metastasis; Mice; Mice, Inbred BALB C; nano‐pulse stimulation; Neoplasm Metastasis; Remission; Stimulation; Suppressor cells; tumor ablation; breast cancer; nano-pulse stimulation; dendritic cell activation; immune response; tumor ablation; immunogenic cell death
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.31071

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.
What's new?
Nanosecond‐length electric pulses can induce cell death and, in animal models, have been shown to cause tumor remission. Because nanoelectroablation is rapid and minimally invasive, it is an appealing alternative to conventional ablation strategies. This study shows that nano‐pulse stimulation (NPS), which stimulates an immune response upon tumor ablation, elicits potent antitumor immunity in an otherwise poorly immunogenic 4T1‐Luc mouse mammary carcinoma model. NPS treatment destroyed the tumor microenvironment, causing significant declines in populations of tumor‐derived immune suppressor cells and reduced distant metastases. Treated animals were immune to a second tumor challenge, suggesting that NPS produces long‐term antitumor memory.