title: 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.
authors.affiliation: Department of Immunology and Laboratory Immunology, Jiangsu University, Zhenjiang, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.forename: Chaoming
authors.initials: C
authors.lastname: Mao
authors.forename: Jia
authors.initials: J
authors.lastname: Tong
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Wu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jiao
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D047368:Tumor Burden / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C478966:Tnfsf18 protein, mouse; D048069:Tumor Necrosis Factors; D007371:Interferon-gamma