Intratumoral INF-γ triggers an antiviral state in GL261 tumor cells: a major hurdle to overcome for oncolytic vaccinia virus therapy of cancer.
Oncolytic vaccinia virus (VACV) therapy is an alternative treatment option for glioblastoma multiforme. Here, we used a comparison of different tumor locations and different immunologic and genetic backgrounds to determine the replication efficacy and oncolytic potential of the VACV LIVP 1.1.1, an attenuated wild-type isolate of the Lister strain, in murine GL261 glioma models. With this approach, we expected to identify microenvironmental factors, which may be decisive for failure or success of oncolytic VACV therapy. We found that GL261 glioma cells implanted subcutaneously or orthotopically into Balb/c athymic, C57BL/6 athymic, or C57BL/6 wild-type mice formed individual tumors that respond to oncolytic VACV therapy with different outcomes. Surprisingly, only Balb/c athymic mice with subcutaneous tumors supported viral replication. We identified intratumoral IFN-γ expression levels that upregulate MHCII expression on GL261 cells in C57BL/6 wild-type mice associated with a non-permissive status of the tumor cells. Moreover, this IFN-γ-induced tumor cell phenotype was reversible.
Department of Biochemistry, Biocenter, University of Wuerzburg , Wuerzburg, Germany.
Christina
C
Kober
Department of Biochemistry, Biocenter, University of Wuerzburg, Wuerzburg, Germany; Department of Anesthesia and Critical Care, University Hospital of Wuerzburg, Wuerzburg, Germany.
Stephanie
S
Weibel
Department of Biochemistry, Biocenter, University of Wuerzburg , Wuerzburg, Germany.
Susanne
S
Rohn
Department of Biochemistry, Biocenter, University of Wuerzburg , Wuerzburg, Germany.
Lorenz
L
Kirscher
Department of Biochemistry, Biocenter, University of Wuerzburg, Wuerzburg, Germany; Rudolf Virchow Center for Experimental Biomedicine and Institute for Molecular Infection Biology, University of Wuerzburg, Wuerzburg, Germany; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, USA; Genelux Corporation, San Diego Science Center, San Diego, California, USA.
Aladar A
AA
Szalay