Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer

An ineffective tumor-specific immune response from inadequate/incompetent a ntigen presentation could contribute to the failure in tumor control and it s dissemination. Dendritic cells (DCs) have been shown to present antigen f rom apoptotic cells, We hypothesized that Flt3-ligand (Flt3L) therapy, whic h expands DCs in vivo, in combination with local tumor radiotherapy (RT), s hould improve antigen presentation from dying, irradiated tumor cells. RT Flt3L reduced pulmonary metastases in a murine model of Lewis lung carcino ma and significantly improved survival in C57BI/6 mice with established foo tpad tumors, Mice treated with Flt3L alone showed delayed tumor growth but eventually succumbed to tumor progression. The combination therapy of RT Flt3L failed to impact survival in immunodeficient athymic mice, implicatin g the role of T cells in prolonging survival. These results support an attr active strategy of sequential RT and immunotherapy with Flt3L to enhance tu mor antigen presentation, which may produce therapeutic responses against d isseminated cancer and improvement in survival.