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Mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors

Alessandra Rossi1, Olga N Pakhomova1, Andrei G Pakhomov1

  • 1Old Dominion University, Frank Reidy Research Center for Bioelectrics, Norfolk, VA, 23508, USA.

Scientific Reports
|January 25, 2019
PubMed

Insights

Nanosecond pulsed electric fields (nsPEF) induce necrosis, not immunogenic cell death, in melanoma tumors. nsPEF treatment restored natural antitumor immunity but did not enhance it, offering a potential therapeutic avenue.

Area of Science:

  • Oncology
  • Immunology
  • Biophysics

Background:

  • Cancer treatments can restore anticancer immunosurveillance via immunogenic cell death (ICD).
  • Nanosecond pulsed electric fields (nsPEF) are effective in ablating melanoma tumors.

Purpose of the Study:

  • Investigate nsPEF-induced cell death mechanisms and immunogenicity in B16F10 melanoma tumors.
  • Determine if nsPEF triggers ICD or other cell death pathways.

Main Methods:

  • In vitro and in vivo nsPEF treatment of B16F10 melanoma cells and tumors.
  • Assessed cell death markers, including caspase activation, PARP cleavage, necroptosis, and autophagy.
  • Compared antitumor immunity in nsPEF-treated, surgically treated, and naive animals.

Main Results:

  • nsPEF induced rapid, dose-dependent cell death via necrosis, without caspase activation, PARP cleavage, necroptosis, or autophagy.
  • Both nsPEF ablation and surgical removal of tumors partially protected animals from tumor recurrence.
  • nsPEF treatment restored, but did not boost, the host's natural antitumor immunity.

Conclusions:

  • Necrosis is the primary cell death mechanism induced by nsPEF in B16F10 melanoma.
  • nsPEF treatment can restore dormant antitumor immunity, suggesting potential therapeutic applications.
  • Further research is needed to optimize nsPEF for enhanced immunogenic responses in cancer therapy.

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