Oxidation of Innate Immune Checkpoint CD47 on Cancer Cells with Non-Thermal Plasma

Abstract

Non-thermal plasma (NTP) therapy has been emerging as a promising cancer treatment strategy, and recently, its ability to locally induce immunogenic cancer cell death is being unraveled. We hypothesized that the chemical species produced by NTP reduce immunosuppressive surface proteins and checkpoints that are overexpressed on cancerous cells. Here, 3D in vitro tumor models, an in vivo mouse model, and molecular dynamics simulations are used to investigate the effect of NTP on CD47, a key innate immune checkpoint. CD47 is immediately modulated after NTP treatment and simulations reveal the potential oxidized salt-bridges responsible for conformational changes. Umbrella sampling simulations of CD47 with its receptor, signal-regulatory protein alpha (SIRPα), demonstrate that the induced-conformational changes reduce its binding affinity. Taken together, this work provides new insight into fundamental, chemical NTP-cancer cell interaction mechanisms and a previously overlooked advantage of present NTP cancer therapy: reducing immunosuppressive signals on the surface of cancer cells.

Toward defining plasma treatment dose: The role of plasma treatment energy of pulsed‐dielectric barrier discharge in dictating in vitro biological responses

“…A microsecond‐pulsed DBD plasma system was chosen for this study, unless otherwise specified, based on our previous experience with this system for cancer treatment. [ 26 ] The power supply was custom built (Megaimpulse Ltd.), producing a 2‐µs pulse (~30 kV) with a rise time of 1─1.5 µs. This system has been shown to be effective for the treatment of three‐dimensional tumors in vitro and in vivo.…”

Auranofin and Cold Atmospheric Plasma Synergize to Trigger Distinct Cell Death Mechanisms and Immunogenic Responses in Glioblastoma

“…A microsecond-pulsed dielectric barrier discharge (DBD) system which was previously described [7,25] was used for the CAP treatments. Briefly, a microsecond pulser (Megaimpulse Ltd., Russia) generated a 30 kV output pulse with the rise time fixed within 1-1.5 µs and a pulse width of 2 µs.…”

Murine Macrophages Modulate Their Inflammatory Profile in Response to Gas Plasma-Inactivated Pancreatic Cancer Cells

“…This may also affect other targets of the TME, such as thiols [ 57 , 58 , 59 ] and extracellular matrix hyaluron [ 60 ], that upon plasma treatment were recently identified to show disrupted binding to its receptor CD44 [ 61 ]. The second is long-term effects on the expression levels of immune-relevant ligands and receptors, as we and others have reported recently [ 54 , 62 , 63 , 64 , 65 , 66 ]. Importantly, both events may combine during gas plasma exposure of cancer tissue to promote antitumor immunity [ 67 , 68 ].…”

“…This was shown in pancreatic cancer, being intertwined by the efficacy of checkpoint immunotherapy against the PD-1/PD-L1 axis [ 52 ]. CD47 is another recently reported immune checkpoint [ 53 ] that was recently identified to be altered in response to gas plasma treatment [ 54 ]. This and the current work add to important routes for immune-relevant effects of gas plasma treatment of cancer cells.…”