Broad antitumor protection by dendritic cells administered to CD8[alpha] knock out mice

• Published in: Cancer immunology, immunotherapy immunotherapy, 2006-06, Vol.55 (6), p.663
• Main Authors: Ribas, Antoni, Vo, Dan D, Weeks, David L, Comin-Anduix, Begoña, Schumacher, Lana Y, Garban, Hermes J, McLean, Colin, Yang, JinQuan, Dissette, Vivian B, Peraza, Pedro, Owens, Sharla K, McBride, William H, Glaspy, John A, Economou, James S
• Format: Article
• Language: English
• Subjects: Antigens; Cytokines; Dendritic cells; Oncology; Tumors
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-005-0065-y

Dendritic cell (DC) administration to CD8α knock-out (CD8αKO) 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. CD8αKO 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 CD8αKO 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 CD8αKO 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 CD8αKO mice signals directly to PI3-K, but is distinct from NKG2D.