Abstract
Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with an immunological dimension, successful antigen presentation and inflammation modulation is a key hallmark to elicit antitumor immunity. Dendritic cells (DCs) are critical for this task. However, the inflammatory consequences of DCs following plasma exposure are unknown. To this end, human monocyte-derived DCs (moDCs) were expanded from isolated human primary monocytes; exposed to plasma; and their metabolic activity, surface marker expression, and cytokine profiles were analyzed. As controls, hydrogen peroxide, hypochlorous acid, and peroxynitrite were used. Among all types of ROS/RNS-mediated treatments, plasma exposure exerted the most notable increase of activation markers at 24 h such as CD25, CD40, and CD83 known to be crucial for T cell costimulation. Moreover, the treatments increased interleukin (IL)-1α, IL-6, and IL-23. Altogether, this study suggests plasma treatment augmenting costimulatory ligand and cytokine expression in human moDCs, which might exert beneficial effects in the tumor microenvironment.
Highlights
The resolution of many diseases is controlled by precise modulation of inflammation [1,2,3]
To estimate the sensitivity of monocyte-derived DCs (moDCs) compared to lymphocytes, cell suspensions were treated together, and the number of dead cells was analyzed for each population separately (Figure 1c)
It was found that lymphocytes were markedly more sensitive to argon plasmainduced cytotoxic effects compared to the moDCs (Figure 1d)
Summary
The resolution of many diseases is controlled by precise modulation of inflammation [1,2,3]. Pro-inflammatory responses help to promote pathogen clearance and antigen presentation to engage adaptive immunity, while anti-inflammatory responses often counterbalance preceding inflammation, which—if left unchecked—lead to tissue damage and cellular dysfunction. Cells of the innate immune system critically modulate inflammatory responses and provide the link between a pathological condition, e.g., infection or cancer and adaptive immune responses that can, for instance, target infected or malignant cells. Two major DC subsets exist: conventional DCs (cDCs) and plasmacytoid DCs (pDCs). The former are characterized by toll-like receptor (TLR) 2 and 4 expression and can be further divided into cDC-1, which are more abundant and provide major stimulus for Dendritic cells (DCs) are the most prominent example of providing activating antigens for T cell stimulation, which is why these cells are a member of the professional antigen-presenting cells (APCs) family [4].
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