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Updated: Jun 10, 2025
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
Effect of plasma-induced oxidation on NK cell immune checkpoint ligands: A computational-experimental approach
Pepijn Heirman1, Hanne Verswyvel2, Mauranne Bauwens2
1Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium.
Abstract:
Non-thermal plasma (NTP) shows promise as a potent anti-cancer therapy with both cytotoxic and immunomodulatory effects. In this study, we investigate the chemical and biological effects of NTP-induced oxidation on several key, determinant immune checkpoints of natural killer (NK) cell function. We used molecular dynamics (MD) and umbrella sampling simulations to investigate the effect of NTP-induced oxidative changes on the MHC-I complexes HLA-Cw4 and HLA-E. Our simulations indicate that these chemical alterations do not significantly affect the binding affinity of these markers to their corresponding NK cell receptor, which is supported with experimental read-outs of ligand expression on human head and neck squamous cell carcinoma cells after NTP application. Broadening our scope to other key ligands for NK cell reactivity, we demonstrate rapid reduction in CD155 and CD112, target ligands of the inhibitory TIGIT axis, and in immune checkpoint CD73 immediately after treatment. Besides these transient chemical alterations, the reactive species in NTP cause a cascade of downstream cellular reactions. This is underlined by the upregulation of the stress proteins MICA/B, potent ligands for NK cell activation, 24 h post treatment. Taken together, this work corroborates the immunomodulatory potential of NTP, and sheds light on the interaction mechanisms between NTP and cancer cells.
Insights
Non-thermal plasma (NTP) therapy modulates natural killer (NK) cell function by altering immune checkpoints. NTP treatment reduces inhibitory ligands while upregulating activating ligands on cancer cells, supporting its immunomodulatory potential.
Area of Science:
- Immunology
- Plasma Physics
- Biochemistry
Background:
- Non-thermal plasma (NTP) is a promising anti-cancer therapy with cytotoxic and immunomodulatory effects.
- Natural killer (NK) cells are crucial for anti-cancer immunity, with their function regulated by immune checkpoints.
Purpose of the Study:
- To investigate the chemical and biological effects of NTP-induced oxidation on key NK cell immune checkpoints.
- To elucidate the interaction mechanisms between NTP and cancer cells at the molecular level.
Main Methods:
- Molecular dynamics (MD) and umbrella sampling simulations were used to study oxidative changes on MHC-I complexes (HLA-Cw4, HLA-E).
- Experimental read-outs assessed ligand expression on human head and neck squamous cell carcinoma cells post-NTP treatment.
- Changes in immune checkpoint ligands (CD155, CD112, CD73) and stress proteins (MICA/B) were analyzed.
Main Results:
- NTP-induced oxidative changes did not significantly affect the binding affinity of HLA-Cw4 and HLA-E to NK cell receptors.
- Rapid reduction in inhibitory ligands CD155, CD112, and immune checkpoint CD73 was observed immediately after NTP treatment.
- Upregulation of activating ligands MICA/B occurred 24 hours post-treatment, indicating downstream cellular reactions.
Conclusions:
- NTP exhibits significant immunomodulatory potential by transiently altering inhibitory NK cell ligands and inducing delayed upregulation of activating ligands.
- This study provides insights into the mechanisms by which NTP interacts with cancer cells to modulate NK cell-mediated immunity.
