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Int. J. Mol. Sci. 2017, 18(5), 966; doi:10.3390/ijms18050966

Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells through Intracellular Oxidative Stress

1
C. & J. Nyheim Plasma Institute, Drexel University, Philadelphia, PA 19104, USA
2
Plasma Bioscience Research Center, Kwangwoon University, Seoul 139791, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Hsueh-Wei Chang
Received: 1 March 2017 / Revised: 27 April 2017 / Accepted: 28 April 2017 / Published: 3 May 2017
(This article belongs to the Special Issue Tumor Targeting Therapy and Selective Killing)
View Full-Text   |   Download PDF [4258 KB, uploaded 3 May 2017]   |  

Abstract

A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death. We assessed changes to the intracellular oxidative environment after plasma treatment and correlated it to emission of two danger signals: surface-exposed calreticulin and secreted adenosine triphosphate. Plasma-generated reactive oxygen and charged species were recognized as the major effectors of immunogenic cell death. Chemical attenuators of intracellular reactive oxygen species successfully abrogated oxidative stress following plasma treatment and modulated the emission of surface-exposed calreticulin. Secreted danger signals from cells undergoing immunogenic death enhanced the anti-tumor activity of macrophages. This study demonstrated that plasma triggers immunogenic cell death through oxidative stress pathways and highlights its potential development for cancer immunotherapy. View Full-Text
Keywords: non-thermal plasma; cancer immunotherapy; immunogenic cell death; oxidative stress; calreticulin; adenosine triphosphate; plasma immunotherapy; nanosecond-pulsed dielectric barrier discharge non-thermal plasma; cancer immunotherapy; immunogenic cell death; oxidative stress; calreticulin; adenosine triphosphate; plasma immunotherapy; nanosecond-pulsed dielectric barrier discharge
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lin, A.; Truong, B.; Patel, S.; Kaushik, N.; Choi, E.H.; Fridman, G.; Fridman, A.; Miller, V. Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells through Intracellular Oxidative Stress. Int. J. Mol. Sci. 2017, 18, 966.

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