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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Multi-Cohort Transcriptomic Profiling of Medical Gas Plasma-Treated Cancers Reveals the Role of Immunogenic Cell
Antonios Gkantaras1,2, Charalampos Kotzamanidis3, Konstantinos Kyriakidis4
1Laboratory of Biological Chemistry, Medical School, Aristotle University, 54124 Thessaloniki, Greece.
Abstract:
The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The cytotoxic effect on malignant cells has been attributed mainly to biologically active plasma-generated compounds, namely, reactive oxygen and nitrogen species. The intracellular accumulation of reactive oxygen and nitrogen species interferes strongly with the antioxidant defense system of malignant cells, activating multiple signaling cascades and inevitably leading to oxidative stress-induced cell death. This study aims to determine whether plasma-induced cancer cell death operates through a universal molecular mechanism that is independent of the cancer cell type. Using whole transcriptome data, we sought to investigate the activation mechanism of plasma-treated samples in patient-derived prostate cell cultures, melanoma, breast, lymphoma, and lung cancer cells. The results from the standardized single-cohort gene expression analysis and parallel multi-cohort meta-analysis strongly indicate that plasma treatment globally induces cancer cell death through immune-mediated mechanisms, such as interleukin signaling, Toll-like receptor cascades, and MyD88 activation leading to pro-inflammatory cytokine release and tumor antigen presentation.
Insights
Cold atmospheric plasma induces cancer cell death via immune system activation. This study reveals a universal mechanism across diverse cancer types, highlighting potential for novel cancer therapies.
Area of Science:
- Oncology
- Biophysics
- Immunology
Background:
- Cold atmospheric plasma (CAP) shows therapeutic promise in oncology.
- CAP's cytotoxic effects stem from reactive oxygen and nitrogen species (RONS).
- RONS disrupt cancer cell antioxidant defenses, causing oxidative stress and cell death.
Purpose of the Study:
- To investigate if plasma-induced cancer cell death follows a universal, cancer-type-independent molecular mechanism.
- To analyze gene expression data from various patient-derived cancer cell lines treated with CAP.
Main Methods:
- Whole transcriptome analysis of plasma-treated prostate, melanoma, breast, lymphoma, and lung cancer cells.
- Standardized single-cohort gene expression analysis.
- Parallel multi-cohort meta-analysis of gene expression data.
Main Results:
- Plasma treatment universally activates immune-mediated cell death pathways in cancer cells.
- Key activated pathways include interleukin signaling and Toll-like receptor cascades.
- MyD88 activation leads to pro-inflammatory cytokine release and tumor antigen presentation.
Conclusions:
- Plasma-induced cancer cell death is primarily mediated by immune system activation.
- This immune-mediated mechanism is consistent across different cancer cell types.
- Findings suggest CAP as a potential immunotherapy agent for diverse cancers.
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