Oncolytic virus-derived type I interferon restricts CAR T cell therapy.

Autor:	Evgin L; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Huff AL; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Wongthida P; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Thompson J; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Kottke T; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Tonne J; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Schuelke M; Department of Immunology, Mayo Clinic, Rochester, MN, USA., Ayasoufi K; Department of Immunology, Mayo Clinic, Rochester, MN, USA., Driscoll CB; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Shim KG; Department of Immunology, Mayo Clinic, Rochester, MN, USA., Reynolds P; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Monie DD; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Johnson AJ; Department of Immunology, Mayo Clinic, Rochester, MN, USA., Coffey M; Oncolytics Biotech Incorporated, Calgary, Canada., Young SL; Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand., Archer G; Department of Neurosurgery, Duke University, Durham, NC, USA., Sampson J; Department of Neurosurgery, Duke University, Durham, NC, USA., Pulido J; Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA., Perez LS; Department of Neurosurgery, Duke University, Durham, NC, USA., Vile R; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA. vile.richard@mayo.edu.; Department of Immunology, Mayo Clinic, Rochester, MN, USA. vile.richard@mayo.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Jun 24; Vol. 11 (1), pp. 3187. Date of Electronic Publication: 2020 Jun 24.
DOI:	10.1038/s41467-020-17011-z
Abstrakt:	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, VSVmIFNβ 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 VSVmIFNβ. 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu