sion and Promotes Protective Antitumor Immunity

ownload or-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure phocyte activation and homing, resist the development of tumor-specific immunity and hamper the ne response–mediated elimination of cancerous cells. In this report, we show that reovirus virotherverrides such a tumor immune evasion and establishes clinically meaningful antitumor immunity le of protecting against subsequent tumor challenge. Reovirus-mediated destruction of tumor cells tes the recognition of tumor antigens by promoting the display of otherwise inaccessible tumorc immunogenic peptides on the surface of dendritic cells (DC). Furthermore, on exposure to reoviCs produce IL-1α, IL-1β, IL-6, IL-12p40/70, IL-17, CD30L, eotaxin, GM-CSF, KC, MCP-1, MCP-5, , MIG, MIP-1α, RANTES, TNF-α, VCAM-1, VSGF, CXCL-16, AXL, and MCP-2; undergo maturand migrate into the tumor microenvironment along with CD8 T cells. These reovirus-activated DCs cquire the capacity to prime tumor antigen–specific transgenic T cells in vitro and intrinsic antitumor response in vivo. Further, reovirus virotherapy augments the efficacy of DCor T cell–based antiimmunotherapies and synergistically enhances the survival in tumor-bearing mice. Most impor, antitumor cellular immune responses initiated during reovirus oncotherapy protect the host t subsequent tumor challenge in a reovirus-independent but antigen-dependent manner. These reooncotherapy–initiated antitumor immune responses represent an anticancer therapeutic entity that virus can maintain a long-term cancer-free health even after discontinuation of therapy. Mol Cancer Ther; 9(11); OF1–10. ©2010 AACR.