Dendritic cells engineered to express GITRL enhance therapeutic immunity in murine Lewis lung carcinoma

Abstract

Glucocorticoid-induced tumor necrosis factor receptor and its ligand (GITRL) are critically involved in the regulation of immune response. In this study, we aimed to generate bone marrow-derived dendritic cells (BMDCs) transfected with recombinant adenovirus expressing GITRL (pAd-GITRL-BMDCs) and explore their therapeutic efficacy in murine Lewis lung carcinoma. In vitro, pAd-GITRL-BMDCs greatly enhanced effector T cells proliferation but markedly abrogate the suppression of Treg cells. Moreover, vaccination with pAd-GITRL-BMDCs significantly retarded tumor growth, which was accompanied with increased IFN-γ-producing CD8+ T cells and markedly decreased Treg cells in vivo. These findings suggest GITRL could enhance the immune stimulation of DC and might facilitate the potential development of DCs-based anti-tumor therapies.