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Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma
Abraham Lin1, Billy Truong2, Sohil Patel3
1C. & J. Nyheim Plasma Institute, Drexel University, Philadelphia, PA 19104, USA. agl46@glink.drexel.edu.
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.
Insights
Non-thermal plasma induces immunogenic cancer cell death via oxidative stress, enhancing anti-tumor immunity. This approach shows promise for developing novel cancer immunotherapies.
Area of Science:
- Biophysics
- Immunology
- Oncology
Background:
- Non-thermal plasma is a novel tool for cancer immunotherapy.
- Immunogenic cell death (ICD) involves danger signals that promote anti-tumor immunity.
- Oxidative stress is a proposed mechanism underlying ICD.
Purpose of the Study:
- To investigate the role of oxidative stress in plasma-induced ICD.
- To correlate plasma treatment effects on intracellular oxidative stress with ICD danger signal emission.
- To assess the impact of plasma-generated species on cancer cell death and immune response.
Main Methods:
- Exposure of cancer cells to dielectric barrier discharge plasma.
- Assessment of intracellular oxidative stress markers.
- Quantification of surface-exposed calreticulin and secreted adenosine triphosphate (ATP) as danger signals.
- Evaluation of macrophage anti-tumor activity.
Main Results:
- Plasma treatment induced oxidative stress in cancer cells.
- Increased oxidative stress correlated with elevated calreticulin and ATP release.
- Plasma-generated reactive oxygen and charged species were identified as key mediators of ICD.
- Inhibition of oxidative stress reduced danger signal emission.
- Danger signals enhanced macrophage-mediated anti-tumor effects.
Conclusions:
- Dielectric barrier discharge plasma triggers cancer cell immunogenic death through oxidative stress pathways.
- Plasma-induced ICD, mediated by reactive oxygen and charged species, enhances anti-tumor immunity.
- This study supports the potential of non-thermal plasma as a cancer immunotherapy modality.
