Enhanced Antitumor Immunity Elicited by Dendritic Cell Vaccines Is a Result of Their Ability to Engage Both CTL and IFNγ-producing NK Cells.
Activation of cytotoxic T lymphocytes (CTLs) is a primary goal of many cancer vaccination therapies. We have evaluated two vaccination platforms, dendritic cells (DCs) and recombinant adenoviruses (rAds), for their ability to elicit CTL response and antitumor protection. Although rAd was more potent in CTL priming, DC vaccination provided greater protective and therapeutic antitumor activity. Subsequent analyses ruled out the possibility that the two vaccines elicit qualitatively distinct CTL, and demonstrated instead that DCs could better engage natural killer (NK) cells as an additional effector mechanism. We demonstrated that, although both DCs and rAd can stimulate rapid NK expansion, only DC-activated NK cells are able to produce interferon-γ (IFNγ) and mediate antitumor protection. Moreover, our data showed that exogenously delivered DCs preferentially engaged the Mac-1highCD27highNK subset, thereby suggesting that this NK population plays a predominant role in NK:DC interaction. Interestingly, at least 3 days were required for DC-triggered NK cells to acquire effector functions, indicating that a similar priming process operates between T cells and NK cells. Our results suggest that the nature of the vaccine platform can determine the relative involvement of NK and T cells in antitumor immunity, and that methods to augment NK function should be included in vaccination strategies in order to complement CTL-mediated control of tumor growth.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Khalil
K
Karimi
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Jeanette E
JE
Boudreau
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Katie
K
Fraser
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Hongju
H
Liu
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Jordan
J
Delanghe
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Jack
J
Gauldie
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Zhou
Z
Xing
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Jonathan L
JL
Bramson
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: wanyong@mcmaster.ca.
Yonghong
Y
Wan