Abstract 953: Herpes simplex virus thymidine kinase/ganciclovir-mediated apoptotic tumor cells induce anti-tumor immunity

Immune cells can recognize tumor antigen and elicit an adaptive immune response against tumor cells. It has been reported that apoptotic or necrotic death of tumor cells releases tumor antigen stimulating anti-tumor immunity. However, the immune responses against apoptotic tumor cells in vivo are poorly understood. To investigate whether apoptotic tumor cells affect anti-tumor immunity, local immune responses in tumor were evaluated by induction of apoptotic tumor cells with herpes simplex virus thymidine kinase (HSVtk)/ ganciclovir (GCV) system. HSVtk gene transduced tumor cells were resulted in apoptosis in vitro. Administration of GCV triggered apoptosis in HSVtk transfected tumor cells in vivo and regressed the tumor. Comprehensive gene expression analysis of the bulk tumor showed that IFNγ and IL-12 were upregulated. CD8+ T cells were increased in the treatment group compared to the control group. The tumor regression by induction of GCV-triggered apoptosis was inhibited by anti-CD8 depleting antibody. These findings indicate that apoptotic tumor cells induce CD8+ T cell-dependent anti-tumor immunity. Citation Format: Sho Umegaki, Hidekazu Shirota, Chikashi Ishioka. Herpes simplex virus thymidine kinase/ganciclovir-mediated apoptotic tumor cells induce anti-tumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 953.