4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine tumor

The interaction by co-stimulatory molecules 4-1BB and 4-1BB ligand(4-1BBL)plays an important role in the activation,proliferation and differentiation of T lymphocytes.The function of 4-1BB/4-1BBL expressed by the immune cells has been the focus for many tumor immunotherapy efforts.In this study,4-1BBL was expressed in non-immune cells and non-tumor cells,and the role of 4-1BBL in lymphocyte activation and tumor suppression was investigated.The plasmid p4-1BBL containing the full length of mouse 4-1BBL cDNA sequence was constructed,and the plasmid was transfected into baby hamster kidney(BHK)cells and murine muscle cells by means of lipofectin-mediated or naked plasmid DNA injection into the muscle directly.The study demonstrated that the molecule 4-1BBL expressed by BHK cells in vitro could enhance the proliferation and cytotoxicity of lymphocytes,and it could increase the expression level of IL-2 and IFN-γ.The treatment with plasmid p4-1BBL in vivo revealed that the number of CD8+Tcells in the peri-tumoral tissue increased markedly,and the growth rate of the tumor was significantly lower than that of control group.Thesefindings suggest that expression of 4-1BBL by normal cells in the tumor microenvironment can enhance the proliferation and other functions of T lymphocytes.This therapeutic method may provide a promising approach for tumor immunotherapy.