Publication
Title
Oxidation of innate immune checkpoint CD47 on cancer cells with non-thermal plasma
Author
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.
Language
English
Source (journal)
Cancers
Publication
2021
ISSN
2072-6694
DOI
10.3390/CANCERS13030579
Volume/pages
13 :3 (2021) , 15 p.
Article Reference
579
ISI
000614960600001
Pubmed ID
33540720
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Elucidating mechanisms of plasma-induced immunogenic cancer cell death and determining efficacy to elicit anti-tumor immunity: An experimental and computational study
From physical plasma to cellular pathway: a multi-disciplinary approach to unravel the response pathways induced by nonthermal plasma for cancer therapy.
Plasma-based cancer treatment: Atomic level simulations.
Investigation of non-thermal plasma therapy with first-line treatments of recurrent and metastatic head and neck squamous cell carcinoma: a novel combination with platinum-based chemotherapy and immunotherapy.
Investigating fundamental plasma effects on tumor microenvironment through development of a controlled plasma treatment system for clinical cancer therapy.
Proof-of-concept for novel combination strategies with immunotherapy to treat solid tumors.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 25.03.2021
Last edited 21.11.2024
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