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Article

Regulation of Constitutive Interferon-Stimulated Genes (Isgs) in Tumor Cells Contributes to Enhanced Antitumor Response of Newcastle Disease Virus-Infected Tumor Vaccines

1
School of Veterinary Medicine, Rakuno Gakuen University, 582 Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan
2
Department of Infectious Disease, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
*
Author to whom correspondence should be addressed.
Cancers 2018, 10(6), 186; https://doi.org/10.3390/cancers10060186
Received: 9 May 2018 / Revised: 29 May 2018 / Accepted: 29 May 2018 / Published: 6 June 2018
(This article belongs to the Special Issue Oncolytic Virotherapy)
Newcastle disease virus (NDV) is an oncolytic virus. As immunogenicity of tumor cells is enhanced by NDV infection, recombinant NDV-infected tumor vaccines (rNDV-TV) are effective methods for inducing specific immunity. However, several tumor cells resist NDV infection, and tumor specific immunity is not sufficiently induced by rNDV-TV. Therefore, we clarified the factor contributing to the suppression of NDV infection and attempted to improve rNDV-TV. Initially we investigated the correlation between the NDV infection rate and interferon-related gene expression in six murine tumor cell lines. A significant negative correlation was observed between the constitutive gene expression of Interferon-stimulated genes (ISGs) and NDV infectivity. The NDV infection rate was examined in each tumor cell treated with the Janus kinase (JAK) inhibitor ruxolitinib (Rux). Furthermore, we evaluated the Th1 response induction by Rux-treated rNDV-TV (rNDV-TV-Rux). In Rux-treated tumor cells, Oasl2 gene expression was significantly decreased and viral infectivity was increased. In immunized mice, the number of CD8+ cells, and those expressing the IFN-γ gene, were significantly increased as compared with Rux-untreated rNDV-TV. The infectivity of the virus was dependent on the degree of ISGs expression in tumor cells. To remedy for this problem, rNDV-TV-Rux was expected to have a Th1 immune response. View Full-Text
Keywords: Newcastle disease virus; tumor; vaccines; ISG; ruxolitinib Newcastle disease virus; tumor; vaccines; ISG; ruxolitinib
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MDPI and ACS Style

Takamura-Ishii, M.; Nakaya, T.; Hagiwara, K. Regulation of Constitutive Interferon-Stimulated Genes (Isgs) in Tumor Cells Contributes to Enhanced Antitumor Response of Newcastle Disease Virus-Infected Tumor Vaccines. Cancers 2018, 10, 186. https://doi.org/10.3390/cancers10060186

AMA Style

Takamura-Ishii M, Nakaya T, Hagiwara K. Regulation of Constitutive Interferon-Stimulated Genes (Isgs) in Tumor Cells Contributes to Enhanced Antitumor Response of Newcastle Disease Virus-Infected Tumor Vaccines. Cancers. 2018; 10(6):186. https://doi.org/10.3390/cancers10060186

Chicago/Turabian Style

Takamura-Ishii, Mai, Takaaki Nakaya, and Katsuro Hagiwara. 2018. "Regulation of Constitutive Interferon-Stimulated Genes (Isgs) in Tumor Cells Contributes to Enhanced Antitumor Response of Newcastle Disease Virus-Infected Tumor Vaccines" Cancers 10, no. 6: 186. https://doi.org/10.3390/cancers10060186

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