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Success of measles virotherapy in ATL depends on type I interferon secretion and responsiveness.
- Source :
-
Virus research [Virus Res] 2014 Aug 30; Vol. 189, pp. 206-13. Date of Electronic Publication: 2014 Jun 06. - Publication Year :
- 2014
-
Abstract
- Adult T cell leukemia/lymphoma (ATL) is a highly aggressive CD4+/CD25+ T-cell malignancy caused by human T cell lymphotropic virus type 1 (HTLV-1). Previous studies in the MET-1 cell/NOD/SCID mouse model of ATL demonstrated that MET-1 cells are very susceptible to measles virus (MV) oncolytic therapy. To further evaluate the potential of MV therapy in ATL, the susceptibility of several HTLV-1 transformed CD4+ T cell lines (MT-1, MT-2, MT-4 and C8166-45) as well as HTLV-1 negative CD4+ T cell lines (Jurkat and CCRF-CEM) to infection with MV was tested in vitro. All cell lines were permissive to MV infection and subsequent cell death, except MT-1 and CCRF-CEM cells which were susceptible and permissive to MV infection, but resistant to cell death. The resistance to MV-mediated cell death was associated with IFNβ produced by MT-1 and CCRF-CEM cells. Inhibition of IFNβ rendered MT-1 and CCRF-CEM cells susceptible to MV-mediated cell death. Cells susceptible to MV-induced cell death did not produce nor were responsive to IFNβ. Upon infection with Newcastle Disease Virus (NDV), MT-1 and CCRF-CEM but not the susceptible cell lines up-regulated pSTAT-2. In vivo, treatment of tumors induced by MT-1 cell lines which produce IFNβ demonstrated only small increases in mean survival time, while only two treatments prolonged mean survival time in mice with MET-1 tumors deficient in type I interferon production. These results indicate that type I interferon production is closely linked with the inability of tumor cells to respond to type I interferon. Screening of tumor cells for type I interferon could be a useful strategy to select candidate patients for MV virotherapy.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line
Cell Survival
Disease Models, Animal
Female
Humans
Mice, SCID
Survival Analysis
Interferon Type I immunology
Interferon Type I metabolism
Leukemia-Lymphoma, Adult T-Cell immunology
Leukemia-Lymphoma, Adult T-Cell therapy
Measles virus growth & development
Oncolytic Virotherapy methods
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7492
- Volume :
- 189
- Database :
- MEDLINE
- Journal :
- Virus research
- Publication Type :
- Academic Journal
- Accession number :
- 24911240
- Full Text :
- https://doi.org/10.1016/j.virusres.2014.05.025