title: Differential capacity of human interleukin-4 and interferon-α monocyte-derived dendritic cells for cross-presentation of free versus cell-associated antigen.
abstract: Dendritic cells (DC) vaccination is a potent therapeutic approach for inducing tumor-directed immunity, but challenges remain. One of the particular interest is the induction of an immune response targeting multiple (unknown) tumor-associated antigens (TAA), which requires a polyvalent source of TAA. Previously, we described the preferred use of apoptotic cell-derived blebs over the larger apoptotic cell remnants, as a source of TAA for both in situ loading of skin-resident DC and in vitro loading of monocyte-derived DC (MoDC). Recent reports suggest that MoDC cultured in the presence of GM-CSF supplemented with IFNα (IFNα MoDC), as compared to IL-4 (IL-4 MoDC), have an increased capacity to cross-present antigen to CD8(+) T cells. As culture conditions, maturation methods and antigen sources differ between the conducted studies, we analyzed the functional differences between IL-4 MoDC and IFNα MoDC, loaded with blebs, in a head-to-head comparison using commonly used protocols. Our data show that both MoDC types are potent (cross-) primers of CD8(+) T cells. Whereas IFNα MoDC were more potent in their capacity to cross-present a 25-mer MART-1 synthetic long peptide (SLP) to a MART-1aa26-35 recognizing CD8(+) T cell line, IL-4 MoDC proved more potent cross-primers of antigen-specific CD8(+) T cells when loaded with blebs. The latter is likely due to the observed greater capacity of IL-4 MoDC to ingest apoptotic blebs. In conclusion, our data indicate the use of IFNα MoDC over IL-4 MoDC in the context of DC vaccination with SLP, whereas IL-4 MoDC are preferred for vaccination with bleb-derived antigens.
authors.affiliation: Department of Hematology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
authors.forename: Jurjen M
authors.initials: JM
authors.lastname: Ruben
authors.affiliation: Department of Hematology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.affiliation: Department of Hematology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.affiliation: Department of Pathology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Hooijberg
authors.affiliation: Department of Hematology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.affiliation: Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.affiliation: Department of Hematology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands. a.vandeloosdrecht@vumc.nl.
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D058965:MART-1 Antigen / Q000276:immunology; D009000:Monocytes / Q000166:cytology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C508598:IL4 protein, human; D016898:Interferon-alpha; D058965:MART-1 Antigen; D015847:Interleukin-4
keywords: Antigen presentation; IFNα; IL-4; Monocyte-derived dendritic cell; Vaccination