title: Parvovirus H-1-induced tumor cell death enhances human immune response in vitro via increased phagocytosis, maturation, and cross-presentation by dendritic cells.
abstract: Oncotropic and oncolytic viruses have attracted high attention as antitumor agents because they preferentially kill cancer cells in vitro and reduce the incidence of spontaneous, induced, or implanted animal tumors. Some autonomous parvoviruses (H-1, minute virus of mice) and derived recombinant vectors are currently under preclinical evaluation. Still not fully understood, their antitumor properties involve more than just tumor cell killing. Because wild-type parvovirus-mediated tumor cell lysates (TCLs) may trigger antigen-presenting cells (APCs) to augment the host immune repertoire, we analyzed phagocytosis, maturation, and crosspresentation of H-1-induced TCLs by human dendritic cells (DCs). We first established H-1-mediated oncolysis in two HLA-A2(+) and A2(-) variant melanoma cell clones. Monocyte-derived immature DCs phagocytosed H- 1-infected TCLs as well as ultraviolet-induced apoptotic TCLs and better than freeze-thaw-induced necrotic TCLs. Immature DCs incubated with H-1-induced TCLs acquired specific maturation markers comparable to a standard cytokine cocktail. Furthermore, A2(+) DCs pulsed with H-1-infected A2(-) TCLs cross-presented melanoma antigens to specific cytotoxic T lymphocytes (CTLs) and released proinflammatory cytokines. This shows for the first time that tumor cell killing by a wild-type oncolytic virus directly stimulates human APCs and CTLs. Because H-1-infected tumors enhance the immune repertoire, the clinical perspectives of parvoviral vectors are even more promising.
authors.affiliation: Department of Medicine I, Johannes Gutenberg University Mainz, Germany.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Moehler
authors.forename: Maja
authors.initials: M
authors.lastname: Zeidler
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wilsberg
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelis
authors.forename: Thomas
authors.initials: T
authors.lastname: Woelfel
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Michael
authors.initials: M
authors.lastname: Heike
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis; D002454:Cell Differentiation; D045142:Cross-Priming; D015925:Cryopreservation; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D017992:Parvovirus / Q000276:immunology* / Q000472:pathogenicity*; D010587:Phagocytosis; D012878:Skin Neoplasms / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen