Plasma Treatment of Ovarian Cancer Cells Mitigates Their Immuno-Modulatory Products Active on THP-1 Monocytes

Abstract

Cancers modulate their microenvironment to favor their growth. In particular, monocytes and macrophages are targeted by immuno-modulatory molecules installed by adjacent tumor cells such as ovarian carcinomas. Cold physical plasma has recently gained attention as innovative tumor therapy. We confirmed this for the OVCAR-3 and SKOV-3 ovarian cancer cell lines in a caspase 3/7 independent and dependent manner, respectively. To elaborate whether plasma exposure interferes with their immunomodulatory properties, supernatants of control and plasma-treated tumor cells were added to human THP-1 monocyte cultures. In the latter, modest effects on intracellular oxidation or short-term metabolic activity were observed. By contrast, supernatants of plasma-treated cancer cells abrogated significant changes in morphological and phenotypic features of THP-1 cells compared to those cultured with supernatants of non-treated tumor cell counterparts. This included cell motility and morphology, and modulated expression patterns of nine cell surface markers known to be involved in monocyte activation. This was particularly pronounced in SKOV-3 cells. Further analysis of tumor cell supernatants indicated roles of small particles and interleukin 8 and 18, with MCP1 presumably driving activation in monocytes. Altogether, our results suggest plasma treatment to alleviate immunomodulatory secretory products of ovarian cancer cells is important for driving a distinct myeloid cell phenotype.

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

“…Several studies by others and us have observed plasma-induced tumor cell death before [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98]. Kumar and colleagues observed in several pancreatic cancer cell lines an increase in apoptosis concomitant with downregulation of MAPK7, BCL2, and CHK1 [99].…”

Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments

“…These signals can be transmitted using soluble molecules, communication junctions (ion channels, pannexins, gap junctions and chemical synapses), occluding junctions (tight junctions) and anchoring junctions (adherens, desmosomes, focal adhesions, and hemidesmosomes) ( Table 2). The expression of soluble cues, such as chemokines, cytokines, and growth factors, are directly affected by the oxidative stress induced by plasma, as demonstrated before in cancer and immune cells [134,194,195]. In particular, tumour cells exposed to plasma or plasma-treated medium can induce a bystander effect that leads to cell death in the untreated neighbouring population, a process mediated by the generation of secondary 1 O 2 and inactivation of membrane-bound catalase, as discussed in Section 2 [60,97].…”

“…The messages sent between cells can also be transmitted via tunnelling nanotubes and extracellular vesicles (EVs) that allow cargo exchange between cells located at short or long distances. Interestingly, plasma was able to hinder the formation of extracellular vesicles produced by ovarian cancer cells [195], which cargoes could stimulate pro-oncogenic responses and therapy resistance in neighbouring cancer cells. This is particularly important in the TME, as the crosstalk between malignant and stromal cells participates in the regulation of proliferation, angiogenesis, evasion of cells of the immune system and cell recruitment.…”

“…Increased number of EVs released by THP-1 and PMN* [216]. Less EVs produced by plasma-treated OVCAR-3 and SKOV-3 ovarian cancer cells [195]. Induced formation of apoptotic bodies [26,217,218] Tumour cells produce high number of EVs with altered redox balance and ROS levels.…”

Low Temperature Plasma Jets: Characterization and Biomedical Applications

“…The second part of the book is a collection of 8 papers published in the special issue on plasma medicine. The first paper is an introductory review of the field of plasma medicine [52]; some of the following papers discuss the applications of various plasma jets for cancer treatment, including triple-negative breast cancer cells, ovarian cancer cells, and the manner in which plasma can decrease the viability of malignant solid tumors cells [53][54][55]. One paper presents a performance evaluation of three plasma sources/jets [56], while two other papers discuss how plasma modulates the responsiveness of human macrophages and cellular glucose uptake [57,58].…”