Abstract B42: Role of TRAIL signaling in tumor killing

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an endogenous ligand, which plays role in immune surveillance and anti-tumor immunity. Binding of TRAIL to its death receptor (DR4 or DR5) leads to receptor oligomerization and recruitment of the death-inducing signaling complex (DISC), activates the caspase-8 and its downstream caspase cascade and ultimately leads to cell death. Although TRAIL induces apoptosis in many tumor cell lines, almost all normal cells are insensitive to TRAIL-induced cell death. The physiological role of TRAIL remains to be elucidated. Recently, scientists have turned their attention to the emerging role of TRAIL in modulating immune responses. TRAIL administration induced anti-inflammatory effects in several autoimmune animal models. All these results suggest an apoptosis-independent role of TRAIL in the immune system. In this study, we studied the role of TRAIL signaling in immune resistance to tumor growth by using the TRAILR-R knockout mice. We demonstrated TRAIL suppressed T cell activation stimulated by anti-CD3/CD28. T cells from TRAIL-R knockout mice resisted to these effects and were with higher proliferation and cytokine production capability to anti-CD3/CD28 stimulation. However, when the melanoma cell lines B16-F10 were inoculated, there was enhanced tumor growth in TRAIL-R knockout mice compared to the wild type control. This finding suggests TRAIL/TRAIL-R interaction may play a role in host against tumor growth. The immunophenotype of the tumor infiltrating lymphocytes and cytokine production are analyzed. Apoptosis and activation of caspases of tumor cells and infiltrating immune cells are also characterized. This study will help to elucidate the role of TRAIL signaling in tumor killing and immune surveillance. Citation Format: Shih-Hong Siao, Ping-Ning Hsu. Role of TRAIL signaling in tumor killing. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B42.