title: Broad antitumor protection by dendritic cells administered to CD8alpha knock out mice.
abstract: Dendritic cell (DC) administration to CD8alpha knock-out (CD8alphaKO) mice results in a strong antigen-non-specific protection to a B16 murine melanoma tumor challenge. This response is mediated by lytic NK cells and cytokine-producing CD4 cells. We aimed to determine the signals that guide tumor targeting of this response. CD8alphaKO mice in the C57BL/6 background received subcutaneous (s.c.) injections of immature DC. Mice were challenged in vivo or assayed for lytic activity in vitro to a panel of syngeneic tumors with different levels of MHC class I expression. These studies support the following conclusions: (1) DC administration to CD8alphaKO mice results in protective in vivo responses to syngeneic tumors from epithelial, neuroectodermal and hematopoietic origin; in vivo protection is independent of the level of MHC classes I and II expression. (2) The in vitro lytic activity of DC-activated NK cells from CD8alphaKO mice has sensitive and insensitive targets, which is independent of the cell lineage or the level of inhibitory self-MHC surface molecules. (3) In sensitive targets a putative activating NK ligand in DC-stimulated NK cells from CD8alphaKO mice signals directly to PI3-K, but is distinct from NKG2D.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, 90095, USA. aribas@mednet.ucla.edu
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Dan D
authors.initials: DD
authors.lastname: Vo
authors.forename: David L
authors.initials: DL
authors.lastname: Weeks
authors.forename: Begoña
authors.initials: B
authors.lastname: Comin-Anduix
authors.forename: Lana Y
authors.initials: LY
authors.lastname: Schumacher
authors.forename: Hermes J
authors.initials: HJ
authors.lastname: Garban
authors.forename: Colin
authors.initials: C
authors.lastname: McLean
authors.forename: Jinquan
authors.initials: J
authors.lastname: Yang
authors.forename: Vivian B
authors.initials: VB
authors.lastname: Dissette
authors.forename: Pedro
authors.initials: P
authors.lastname: Peraza
authors.forename: Sharla K
authors.initials: SK
authors.lastname: Owens
authors.forename: William H
authors.initials: WH
authors.lastname: McBride
authors.forename: John A
authors.initials: JA
authors.lastname: Glaspy
authors.forename: James S
authors.initials: JS
authors.lastname: Economou
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D019869:Phosphatidylinositol 3-Kinases