Effect of plasma-induced oxidation on NK cell immune checkpoint ligands: A computational-experimental approach
Pepijn Heirman,
Hanne Verswyvel,
Mauranne Bauwens,
Maksudbek Yusupov,
Jorrit De Waele,
Abraham Lin,
Evelien Smits,
Annemie Bogaerts
Affiliations
Pepijn Heirman
Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium
Hanne Verswyvel
Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, 2610, Antwerp, Wilrijk, Belgium; Corresponding author. Research group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium.
Mauranne Bauwens
Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, 2610, Antwerp, Wilrijk, Belgium
Maksudbek Yusupov
Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium; Institute of Fundamental and Applied Research, National Research University TIIAME, 100000, Tashkent, Uzbekistan; Laboratory of Experimental Biophysics, Center for Advanced Technologies, 100174, Tashkent, Uzbekistan
Jorrit De Waele
Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, 2610, Antwerp, Wilrijk, Belgium
Abraham Lin
Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, 2610, Antwerp, Wilrijk, Belgium
Evelien Smits
Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, 2610, Antwerp, Wilrijk, Belgium
Annemie Bogaerts
Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Wilrijk, Belgium
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.
