title: Antigen-independent immune responses after dendritic cell vaccination.
abstract: The ability of cultured, antigen-loaded dendritic cells (DCs) to induce antigen-specific T cell immunity in vivo has previously been demonstrated and confirmed. Immune monitoring naturally focuses on immunity against vaccine antigens and may thus ignore other effects of DC vaccination. Here we therefore focused on antigen-independent responses induced by DC vaccination of renal cell carcinoma patients. In addition to the anticipated response against the vaccine antigen KLH, vaccination with CD83(+) monocyte-derived DCs resulted in a strong increase in the ex vivo proliferative and cytokine responses of PBMCs stimulated with LPS or BCG. In addition, LPS strongly enhanced the KLH-induced proliferative and cytokine response of PBMCs. Moreover, proliferative and cytokine responses of PBMCs stimulated with the homeostatic cytokines IL-7 and IL-15 were also clearly enhanced after DC vaccination. In contrast to LPS induced proliferation, which is well known to depend on monocytes, IL-7 induced proliferation was substantially enhanced after monocyte depletion indicating that monocytes limit IL-7 induced lymphocyte expansion. Our data indicate that DC vaccination leads to an increase in the ex vivo responsiveness of patient PBMCs consistent with a DC vaccination induced enhancement of T cell memory. Our findings also suggest that incorporation of bacterial components and homeostatic cytokines into immunotherapy protocols may be useful in order to enhance the efficacy of DC vaccination and that monocytes may limit DC vaccination induced immunity.
authors.affiliation: Department of Urology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Leonhartsberger
authors.forename: Reinhold
authors.initials: R
authors.lastname: Ramoner
authors.forename: Thomas
authors.initials: T
authors.lastname: Putz
authors.forename: Hubert
authors.initials: H
authors.lastname: Gander
authors.forename: Andrea
authors.initials: A
authors.lastname: Rahm
authors.forename: Claudia
authors.initials: C
authors.lastname: Falkensammer
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Martin
authors.initials: M
authors.lastname: Thurnher
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D009163:Mycobacterium bovis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D019409:Interleukin-15; D015851:Interleukin-7; D008070:Lipopolysaccharides