TY - JOUR
T1 - Adenovirally delivered IFN-β exerts antitumor effects through transient T-lymphocyte depletion and Ag-specific T-cell proliferation
AU - Oh, Sang Seok
AU - Moon, Chaerin
AU - Kim, Dong Hyeok
AU - Song, Hyunkeun
AU - Park, Saegwang
AU - Fu, Yangxin
AU - Kim, Kwang Dong
PY - 2012/6
Y1 - 2012/6
N2 - Type I interferons (IFNs), including IFN-β, are known to enhance antigen (Ag) presentation and to promote the expansion, survival and effector function of CD8 + cytotoxic lymphocytes (CTL) during viral infections. Furthermore, IFN-β is a potent candidate for antitumor drugs; however, recombinant IFN-β is too unstable for use in tumor therapy in vivo. In this study, we therefore examined the efficacy and mechanism of exogenous IFN-β as a biomolecule for tumor therapy, using adenovirus encoding IFN-β (Ad-IFNβ) as a therapeutic agent in a mouse model. Ag104L d and 4T1 tumor cells exposed to Ad-IFNβ showed growth retardation and cell death in vitro, and tumor growth as well as tumor metastasis was inhibited in vivo. The Ad-IFNβ-mediated antitumor effect was dependent on CD8 + T cells in vivo, rather than on a direct cytotoxic effect of Ad-IFNβ. Transient T lymphocyte depletion was observed in tumor tissue after intratumoral injection with Ad-IFNβ. Despite the T lymphocyte depletion, the proliferation of Ag-specific CD8 + T cells was increased in Ad-IFNβ-treated mice compared to control virus-treated mice. These results suggest that IFN-β might contribute to the inhibition of tumor growth by depleting Ag-nonspecific T lymphocytes and enhancing proliferation of Ag-specific CD8 + T cells.
AB - Type I interferons (IFNs), including IFN-β, are known to enhance antigen (Ag) presentation and to promote the expansion, survival and effector function of CD8 + cytotoxic lymphocytes (CTL) during viral infections. Furthermore, IFN-β is a potent candidate for antitumor drugs; however, recombinant IFN-β is too unstable for use in tumor therapy in vivo. In this study, we therefore examined the efficacy and mechanism of exogenous IFN-β as a biomolecule for tumor therapy, using adenovirus encoding IFN-β (Ad-IFNβ) as a therapeutic agent in a mouse model. Ag104L d and 4T1 tumor cells exposed to Ad-IFNβ showed growth retardation and cell death in vitro, and tumor growth as well as tumor metastasis was inhibited in vivo. The Ad-IFNβ-mediated antitumor effect was dependent on CD8 + T cells in vivo, rather than on a direct cytotoxic effect of Ad-IFNβ. Transient T lymphocyte depletion was observed in tumor tissue after intratumoral injection with Ad-IFNβ. Despite the T lymphocyte depletion, the proliferation of Ag-specific CD8 + T cells was increased in Ad-IFNβ-treated mice compared to control virus-treated mice. These results suggest that IFN-β might contribute to the inhibition of tumor growth by depleting Ag-nonspecific T lymphocytes and enhancing proliferation of Ag-specific CD8 + T cells.
KW - Adenovirus encoding IFN-β
KW - Antigen-specific CD8 T cell
KW - Transient T lymphocyte depletion
KW - Tumor therapy
UR - http://www.scopus.com/inward/record.url?scp=84860537877&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860537877&partnerID=8YFLogxK
U2 - 10.3892/ijmm.2012.936
DO - 10.3892/ijmm.2012.936
M3 - Article
C2 - 22426464
AN - SCOPUS:84860537877
SN - 1107-3756
VL - 29
SP - 1153
EP - 1157
JO - International journal of molecular medicine
JF - International journal of molecular medicine
IS - 6
ER -