Modification of Antitumor Immunity by Supernatants of oncoytic Herpes Simplex Virus-Infected Squamous Cell Carcinoma Cells

Abstract

Aims: To determine whether the supernatants of oncolytic herpes simplex virus type 1 (HSV-1)-infected squamous cell carcinoma (SCC) cells can stimulate cytotoxic T cells through dendritic cell (DC) maturation, in vitro and in vivo experiments were performed. Introduction: Oncolytic HSV-1 strain RH2 induced immunogenic cell death with the release and surface exposure of damage-associated molecular patterns (DAMPs) in SCC SCCVII cells. The ability of the supernatants of RH2-infected SCCVII cells to activate immune cells was examined. Materials and methods: The supernatants of SCCVII cells infected with RH2 and cultured for 24hrs and mock-infected cells were concentrated to produce Med24 and MedC. Splenocytes were prepared from tumor-bearing mice. Tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) were measured by enzyme-linked immuno sorbent assay (ELISA). Results: The production of IFN-α was increased by a co-culture of CD4+ T cells or CD8+ T cells with Med24-treated DC. In a co-culture with SCCVII cells, the splenocytes of mice treated with an intratumoral injection of Med24 produced more IFN-γ and exhibited greater cytotoxicity than those of MedC-treated mice. The intratumoral injection of Med24 also increased tumor-infiltrating CD8+ T cells. Conclusion: These results suggest that the supernatants of HSV-1 RH2-infected SCC cells include the molecules responsible for the activation of DCs and T cells and promote anti-tumor immunity against SCC.