Generating a T cell tumor-specific immune response in vivo: can flt3-ligand-generated dendritic cells tip the balance?

Abstract

flt3 ligand (FL) is a growth factor that induces hematopoietic progenitor cell and dendritic cell (DC) expansion when administered to mice. Lymphoid-related (CD8α⁺) and myeloid-related (CD8α⁻) DC are transiently expanded in multiple tissues. Treatment of tumor-bearing mice with FL results in slower tumor growth and, in some cases, tumor rejection and the development of tumor-specific T cell immunity. The clinical use of DC as cellular vehicles for tumor antigen presentation to generate a tumor-specific T cell response is under investigation. DC are currently generated ex vivo, pulsed with antigen, and then infused into patients, and much effort is being directed toward optimizing each of these steps. Administration of FL to humans induces a profound increase in circulating DC. The availability of a large number of DC generated in vivo has important implications for tumor immunotherapy approaches.