REVIEW   

Minerva Biotecnologica 2007 September;19(3):91-104

Copyright © 2007 EDIZIONI MINERVA MEDICA

lingua: Inglese

Natural killer cell activation and dendritic cell-based vaccines

Osada T. ^{1, 2, 3}, Clay T. M. ^{1, 2, 3}, Woo C. Y. ^{2, 3, 4}, Morse M. A. ^{2, 3, 4}, Kim Lyerly H. ^{1, 2, 3, 5, 6}

¹ Department of Surgery Duke University Medical Center, Durham, NC, USA 2 Department of Program in Molecular Therapeutics Duke University Medical Center, Durham, NC, USA 3 Comprehensive Cancer Center Duke University Medical Center, Durham, NC, USA 4 Department of Medicine Duke University Medical Center, Durham, NC, USA 5 Department of Pathology Duke University Medical Center, Durham, NC, USA 6 Department of Immunology Duke University Medical Center, Durham, NC, USA

Natural killer (NK) cells are the key players of the innate immune system, which can immediately limit or eliminate dangerous challenges by pathogens or tumor cells to the host. Recent studies have demonstrated the reciprocal activation of NK cell and dendritic cell (DC) through NK-DC interactions, elucidating the functional links between these two cell lineages. More details in NK-DC interactions, such as subsets of cells, molecular pathways involved and the possible anatomical sites, have been investigated and reported. Murine experiments have demonstrated that injection of mature DCs induces rapid recruitment of NK cells to lymph nodes, and that these NK cells provide interferon-g (IFN-g) for type 1 (Th1) priming of T cells. Thus, an increasing body of in vivo evidence is indicating that NK-DC interactions during the early phase of innate immunity can impact the quality and the magnitude of the subsequent adaptive immune response. Importantly, these studies imply that NK cells might not serve merely as cytotoxic effector cells combating virally-infected cells and malignant tumors, but might also play an important role as immunoregulatory cells with a significant influence on adaptive immunity. However, there is a relative paucity of information from the clinical side regarding NK cell function in adaptive immunity, as few DC vaccine studies have attempted to evaluate the antigen-nonspecific, yet potentially clinically-relevant, NK response to immunization. In this article, we will review studies focusing on NK-DC interactions and highlight the most recent clinical findings relating to the potential role of NK cells in DC-based vaccine therapy.