Patient-Derived Human Basal and Cutaneous Squamous Cell Carcinoma Tissues Display Apoptosis and Immunomodulation following Gas Plasma Exposure with a Certified Argon Jet

Abstract

Reactive oxygen species (ROS) have been subject of increasing interest in the pathophysiology and therapy of cancers in recent years. In skin cancer, ROS are involved in UV-induced tumorigenesis and its targeted treatment via, e.g., photodynamic therapy. Another recent technology for topical ROS generation is cold physical plasma, a partially ionized gas expelling dozens of reactive species onto its treatment target. Gas plasma technology is accredited for its wound-healing abilities in Europe, and current clinical evidence suggests that it may have beneficial effects against actinic keratosis. Since the concept of hormesis dictates that low ROS levels perform signaling functions, while high ROS levels cause damage, we investigated herein the antitumor activity of gas plasma in non-melanoma skin cancer. In vitro, gas plasma exposure diminished the metabolic activity, preferentially in squamous cell carcinoma cell (SCC) lines compared to non-malignant HaCaT cells. In patient-derived basal cell carcinoma (BCC) and SCC samples treated with gas plasma ex vivo, increased apoptosis was found in both cancer types. Moreover, the immunomodulatory actions of gas plasma treatment were found affecting, e.g., the expression of CD86 and the number of regulatory T-cells. The supernatants of these ex vivo cultured tumors were quantitatively screened for cytokines, chemokines, and growth factors, identifying CCL5 and GM-CSF, molecules associated with skin cancer metastasis, to be markedly decreased. These findings suggest gas plasma treatment to be an interesting future technology for non-melanoma skin cancer topical therapy.

Cold atmospheric plasma (CAP) treatment increased reactive oxygen and nitrogen species (RONS) levels in tumor samples obtained from patients with low-grade glioma

“…Our study highlights the potential of CAP as a putative adjunct or combinational therapy in lowgrade glioma treatment to improve surgical outcomes by selectively targeting cancer cell death. It is in line with previous studies where they highlighted the effectiveness of CAP jet in promoting cell cycle arrest, apoptosis, and immunomodulation in tissue samples obtained from glioblastoma and basal cell carcinoma patients [54,55].…”

Gas Plasma Exposure of Glioblastoma Is Cytotoxic and Immunomodulatory in Patient-Derived GBM Tissue

“…Intriguingly, we have also found gas plasma-mediated apoptosis induction in patient-derived metastatic melanoma lesions previously [32]. We recently extended these findings to other skin cancers, namely squamous cell carcinoma and basal cell carcinoma [33]. Additionally, primary-patientderived breast cancer cells were demised in response to gas plasma treatment [34].…”

Effect of direct plasma treatment and plasma‐treated liquid on cutaneous squamous cell carcinoma: A proof‐of‐concept study

“…Studies that investigate the efficacy of CAP on cutaneous SCC are limited, and even the existing studies focused on the usage of plasma jet systems. [19,20,42] These studies have mostly focused on the molecular and immunomodulatory mechanisms of CAP in inactivating SCC and have demonstrated the efficacy of CAP through in vivo studies. In our study, we performed a comprehensive analysis of the effects of direct and indirect plasma treatment on SCC cells using a DBD plasma system.…”