title: Enhanced function of cytotoxic T lymphocytes induced by dendritic cells modified with truncated PSMA and 4-1BBL.
abstract: Interactions between costimulatory molecules and their receptors are vital for Ag-presenting dendritic cells (DCs) to initiate T cells activation, expansion and their antitumor immune responses. Augmentation of costimulatory signal due to the interaction of DCs and T cells may amplify, sustain and drive diversity of cytotoxic T lymphocytes (CTLs) and consequently enhance the antitumor response. 4-1BBL/4-1BB is such a pair of costimulatory ligand and receptor, playing an important role in the co-stimulation of CTLs. Previously, we demonstrated that DCs transduced with recombinant adenovirus encoding truncated PSMA (tPSMA) and m4-1BBL could induce prostate cancer regression in mouse models. In the present study, we further explored the adjuvant role of 4-1BBL in modulating CTLs activation induced by tPSMA gene-pulsed DCs. The apoptosis and cytotoxicity against tPSMA expressing RM-1 cells of CTLs were determined. Results showed that tPSMA gene-pulsed DCs effectively induced T lymphocyte activation and cytotoxicity, which was enhanced by upregulated expression of 4-1BBL, displaying better cell viability, lower CTLs apoptosis, higher expression anti-apoptotic protein of Bcl-xL and phosphorylation of P38, enhanced NF-κB activation, as well as more IFN-γ production. These results demonstrated that 4-1BBL may play a significant role in the co-stimulation pathway for Ag-presenting DCs-mediated CTLs activity, which might be a beneficial adjuvant factor for DCs-based cancer immunotherapy.
authors.affiliation: Department of Urology; The First Affiliated Hospital; Chongqing Medical University; Chongqing, P.R. China.
authors.forename: Kuang
authors.initials: K
authors.lastname: Youlin
authors.forename: Zhang
authors.initials: Z
authors.lastname: Li
authors.forename: Gou
authors.initials: G
authors.lastname: Xin
authors.forename: Xiao
authors.initials: X
authors.lastname: Mingchao
authors.forename: Liu
authors.initials: L
authors.lastname: Xiuheng
authors.forename: Weng
authors.initials: W
authors.lastname: Xiaodong
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D053330:4-1BB Ligand; D000954:Antigens, Surface; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: 4-1BBL; costimulatory molecule; cytotoxic T lymphocytes; dendritic cells; prostate cancer