The results showed that splenic MDSCs recovered from PBS-treated tumor-bearing mice significantly suppressed the Ag-specific proliferation of CD8 + T cells. In this study, we examined whether reovirus inhibits the immunosuppressive activity of MDSCs, resulting in efficient activation of immune cells after in vivo administration. Among the various types of cells involved in immunosuppression, it has been revealed that myeloid-derived suppressor cells (MDSCs) are significantly increased in tumor-bearing hosts and play crucial roles in the immunosuppression in tumor-bearing hosts. Recent studies have demonstrated that overcoming an immunosuppressive environment in tumor-bearing hosts is important to achieve efficient activation of antitumor immunity. Oncolytic reovirus, which possesses 10 segments of dsRNA genome, mediates antitumor effects via not only virus replication in a tumor cell-specific manner, but also activation of antitumor immunity however, the mechanism(s) of reovirus-induced activation of antitumor immunity have not been fully elucidated. 8 Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan 9 Laboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Unit, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.7 Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871, Japan and.6 Laboratory of Hepatocyte Differentiation, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.5 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.4 Laboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.3 Laboratory of Vaccine Science, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.2 Laboratory of Adjuvant Innovation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.1 Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.