Non-thermal plasma-induced immunogenic cell death in cancer

Khalili, Marian; Daniels, Lynsey; Lin, Abraham; Krebs, Fred C.; Snook, Adam E.; Bekeschus, Sander; Bowne, Wilbur B.; Miller, Vandana

doi:10.1088/1361-6463/ab31c1

Cited by 66 publications

(50 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Nobel Prize for Medicine or Physiology 2018 for checkpoint cancer immunotherapies has highlighted the importance of the immune system as a critical contributor to target tumor cells [108]. Because plasma treatment is a local therapy possibly modulating the tumor microenvironment, several reports have addressed the possibility of plasma to stimulate immunity to possibly support anticancer treatment [109,110]. Two lines of research are currently pursued to disentangle the effect of plasma treatment in anticancer immunity.…”

Section: Induction Of An Immune Response Through Cap Treatmentmentioning

confidence: 99%

“…One is the ability of plasma to affect immune cells directly, which leads to their activation or selection of specific subpopulations of immune cells, for example [111]. The second is an indirect activation of immune cells via plasma-mediated tumor cell death and pro-inflammatory signals in the microenvironment [109,110].…”

Section: Induction Of An Immune Response Through Cap Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Semmler

Bekeschus

Schäfer

et al. 2020

Cancers

Self Cite

141

127

View full text Add to dashboard Cite

Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice.

show abstract

Section: Induction Of An Immune Response Through Cap Treatmentmentioning

confidence: 99%

Section: Induction Of An Immune Response Through Cap Treatmentmentioning

confidence: 99%

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Semmler

Bekeschus

Schäfer

et al. 2020

Cancers

Self Cite

141

127

View full text Add to dashboard Cite

show abstract

“…When applied at higher doses, these ROS overcome the capacity of tumor cells and activate different cell signaling pathways that culminate in cell death [13,14]. Besides its cytotoxic effect, cold plasma has been described as a potent inducer of the immunogenic cancer cell death (ICD) [15,16]. Here we investigate a new approach to treat malignant melanoma.…”

Section: Introductionmentioning

confidence: 99%

Combination of Gas Plasma and Radiotherapy Has Immunostimulatory Potential and Additive Toxicity in Murine Melanoma Cells in Vitro

Pasqual-Melo

Sagwal

Freund

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Despite continuous advances in therapy, malignant melanoma is still among the deadliest types of cancer. At the same time, owing to its high plasticity and immunogenicity, melanoma is regarded as a model tumor entity when testing new treatment approaches. Cold physical plasma is a novel anticancer tool that utilizes a plethora of reactive oxygen species (ROS) being deposited on the target cells and tissues. To test whether plasma treatment would enhance the toxicity of an established antitumor therapy, ionizing radiation, we combined both physical treatment modalities targeting B16F10 murine melanoma cell in vitro. Repeated rather than single radiotherapy, in combination with gas plasma-introduced ROS, induced apoptosis and cell cycle arrest in an additive fashion. In tendency, gas plasma treatment sensitized the cells to subsequent radiotherapy rather than the other way around. This was concomitant with increased levels of TNFα, IL6, and GM-CSF in supernatants. Murine JAWS dendritic cells cultured in these supernatants showed an increased expression of cell surface activation markers, such as MHCII and CD83. For PD-L1 and PD-L2, increased expression was observed. Our results are the first to suggest an additive therapeutic effect of gas plasma and radiotherapy, and translational tumor models are needed to develop this concept further.

show abstract

“…ROS-induced cancer cell death can also be highly immunogenic [89] (immunogenic cell death, ICD). Plasma treatment can induce ICD as well [90]. Specifically, cells subjected to ICD can foster antigen-specific immune responses against tumor-associated antigens and neoantigens [91][92][93].…”

Section: Introductionmentioning

confidence: 99%

Identification of Two Kinase Inhibitors with Synergistic Toxicity with Low-Dose Hydrogen Peroxide in Colorectal Cancer Cells In vitro

Freund

Liedtke

Miebach

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Colorectal carcinoma is among the most common types of cancers. With this disease, diffuse scattering in the abdominal area (peritoneal carcinosis) often occurs before diagnosis, making surgical removal of the entire malignant tissue impossible due to a large number of tumor nodules. Previous treatment options include radiation and its combination with intraperitoneal heat-induced chemotherapy (HIPEC). Both options have strong side effects and are often poor in therapeutic efficacy. Tumor cells often grow and proliferate dysregulated, with enzymes of the protein kinase family often playing a crucial role. The present study investigated whether a combination of protein kinase inhibitors and low-dose induction of oxidative stress (using hydrogen peroxide, H2O2) has an additive cytotoxic effect on murine, colorectal tumor cells (CT26). Protein kinase inhibitors from a library of 80 substances were used to investigate colorectal cancer cells for their activity, morphology, and immunogenicity (immunogenic cancer cell death, ICD) upon mono or combination. Toxic compounds identified in 2D cultures were confirmed in 3D cultures, and additive cytotoxicity was identified for the substances lavendustin A, GF109203X, and rapamycin. Toxicity was concomitant with cell cycle arrest, but except HMGB1, no increased expression of immunogenic markers was identified with the combination treatment. The results were validated for GF109203X and rapamycin but not lavendustin A in the 3D model of different colorectal (HT29, SW480) and pancreatic cancer cell lines (MiaPaca, Panc01). In conclusion, our in vitro data suggest that combining oxidative stress with chemotherapy would be conceivable to enhance antitumor efficacy in HIPEC.

show abstract

Non-thermal plasma-induced immunogenic cell death in cancer

Cited by 66 publications

References 84 publications

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Combination of Gas Plasma and Radiotherapy Has Immunostimulatory Potential and Additive Toxicity in Murine Melanoma Cells in Vitro

Identification of Two Kinase Inhibitors with Synergistic Toxicity with Low-Dose Hydrogen Peroxide in Colorectal Cancer Cells In vitro

Contact Info

Product

Resources

About