Oxidation of Innate Immune Checkpoint CD47 on Cancer Cells with Non-Thermal Plasma
by
, , , , , , and
Abraham Lin
1,2,*,†
,
Jamoliddin Razzokov
1,3,4,†
,
Hanne Verswyvel
1,2
,
Angela Privat-Maldonado
1,2
,
Joey De Backer
5,
Maksudbek Yusupov
1
,
Edgar Cardenas De La Hoz
6,
Peter Ponsaerts
7,
Evelien Smits
2 and
Annemie Bogaerts
1
1
PLASMANT-Research Group, University of Antwerp, 2610 Antwerpen-Wilrijk, Belgium
2
Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerpen-Wilrijk, Belgium
3
Tashkent Institute of Irrigation and Agricultural Mechanization Engineers, Tashkent 100000, Uzbekistan
4
Department of Physics, National University of Uzbekistan, Tashkent 100174, Uzbekistan
5
Department of Biomedical Sciences, University of Antwerp, 2610 Antwerpen-Wilrijk, Belgium
6
Optical Metrology, 3D Design and Mechanics (Op3Mech) Research Group, University of Antwerp, 2020 Antwerpen, Belgium
7
Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, University of Antwerp, 2610 Antwerpen-Wilrijk, Belgium
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Cancers 2021, 13(3), 579; https://doi.org/10.3390/cancers13030579
Submission received: 14 January 2021
/
Revised: 26 January 2021
/
Accepted: 27 January 2021
/
Published: 2 February 2021
(This article belongs to the Special Issue Advances in Plasma Oncology toward Clinical Translation)
Simple Summary
Non-thermal plasma is being developed for cancer immunotherapy. The aim of our study was to determine the effect of non-thermal plasma on immunosuppressive immune checkpoint, CD47. The direct effect of non-thermal plasma on CD47 was measured in vitro and in vivo, and the mechanism of action was studied in silico. Non-thermal plasma immediately oxidized CD47, suggesting a dual role of non-thermal plasma therapy to simultaneously increase immunogenic signals and reduce immunosuppressive ones.
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.
