Antitumor Effects in Gas Plasma-Treated Patient-Derived Microtissues—An Adjuvant Therapy for Ulcerating Breast Cancer?

Abstract

Despite global research and continuous improvement in therapy, cancer remains a challenging disease globally, substantiating the need for new treatment avenues. Medical gas plasma technology has emerged as a promising approach in oncology in the last years. Several investigations have provided evidence of an antitumor action in vitro and in vivo, including our recent work on plasma-mediated reduction of breast cancer in mice. However, studies of gas plasma exposure on patient-derived tumors with their distinct microenvironment (TME) are scarce. To this end, we here investigated patient-derived breast cancer tissue after gas plasma-treated ex vivo. The tissues were disjoint to pieces smaller than 100 µm, embedded in collagen, and incubated for several days. The viability of the breast cancer tissue clusters and their outgrowth into their gel microenvironment declined with plasma treatment. This was associated with caspase 3-dependent apoptotic cell death, paralleled by an increased expression of the anti-metastatic adhesion molecule epithelial (E)-cadherin. Multiplex chemokine/cytokine analysis revealed a marked decline in the release of the interleukins 6 and 8 (IL-6, IL-8) and monocyte-chemoattractant-protein 1 (MCP) known to promote a cancer-promoting milieu in the TME. In summary, we provide here, for the first time, evidence of a beneficial activity of gas plasma exposure on human patient-derived breast cancer tissue.

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

“…We recently extended these findings to other skin cancers, namely squamous cell carcinoma and basal cell carcinoma [33]. Additionally, primarypatient-derived breast cancer cells were demised in response to gas plasma treatment [34]. While controlled multipatient cancer studies using this technology are still awaited, these ex vivo results together with first case report collections [35] might motivate future clinical…”

The potential of gas plasma technology for targeting breast cancer

“…The reports addressed various questions, ranging from cell death modalities, over combination treatments with existing cancer treatment regimens, to drug re‐sensitization and immunological consequences. Moreover, our recent studies investigated for the first time gas plasma toxicity in patient‐derived breast cancer tissues exposed ex vivo 120 . Markedly, overall similar effects were noted across most studies, independent of the design and engineering of the plasma device used, and dependent on ROS generation of the plasma device.…”

“…Last but not least, breast cancer patient‐derived samples were recently investigated for their release of inflammatory mediators after gas plasma exposure and incubation ex vivo. 120 Besides several significant but small‐scale differences for several cytokines, the largest changes were observed for IL‐6 and IL‐8 (decrease > 100‐fold). Both IL‐6 and IL‐8 are pleiotropic agents described to perform immunosuppressive functions in breast cancer.…”

“… 188 Gas plasma treatment of breast cancer patient‐derived microspheres in collagen was accompanied by elevated E‐cadherin expression. 120 According, decreased migration was reported for gas plasma‐treated breast cancer cells in transwell migration and matrigel invasion as well as 2D time‐lapse video microscopy cell motility assays. 130 This is supported by findings on reduced TRIM31 expression in breast cancer cells following gas plasma exposure, 165 a molecule involved in tumour progression and metastasis.…”

“…Moreover, our recent studies investigated for the first time gas plasma toxicity in patient‐derived breast cancer tissues exposed ex vivo. 120 Markedly, overall similar effects were noted across most studies, independent of the design and engineering of the plasma device used, and dependent on ROS generation of the plasma device. The majority of studies used the cell lines MDA‐MD‐231 and MCF‐7, apart from about a dozen other cell lines utilized to a lesser extent.…”