Oncolytic virus-derived type I interferon restricts CAR T cell therapy.
Nat Commun
; 11(1): 3187, 2020 06 24.
Article
em En
| MEDLINE
| ID: mdl-32581235
ABSTRACT
The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test whether the inflammatory nature of oncolytic viruses and their ability to remodel the tumor microenvironment may help to recruit and potentiate the functionality of CAR T cells. Contrary to our hypothesis, VSVmIFNß infection is associated with attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite inducing a robust proinflammatory shift in the chemokine profile. Mechanistically, type I interferon (IFN) expressed following infection promotes apoptosis, activation, and inhibitory receptor expression, and interferon-insensitive CAR T cells enable combinatorial therapy with VSVmIFNß. Our study uncovers an unexpected mechanism of therapeutic interference, and prompts further investigation into the interaction between CAR T cells and oncolytic viruses to optimize combination therapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Imunoterapia Adotiva
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Interferon beta
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Vírus Oncolíticos
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Receptores de Antígenos Quiméricos
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article