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Enhanced antitumor immunity elicited by dendritic cell vaccines is a result of their ability to engage both CTL and IFN gamma-producing NK cells

(2008) MOLECULAR THERAPY. 16(2). p.411-418
Author
Organization
Abstract
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-gamma (IFN gamma) and mediate antitumor protection. Moreover, our data showed that exogenously delivered DCs preferentially engaged the Mac-1(high)CD27(high) NK 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.
Keywords
IN-VIVO, RECOMBINANT ADENOVIRUS, NATURAL-KILLER-CELLS, T-CELLS, TUMOR, VACCINATION, INNATE, ANTIGEN, RESPONSES, ACTIVATION

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Chicago
Karimi, Khalil, Jeanette E. Boudreau, Katie Fraser, Hongju Liu, Jordan Delanghe, Jack Gauldie, Zhou Xing, Jonathan L. Bramson, and Yonghong Wan. 2008. “Enhanced Antitumor Immunity Elicited by Dendritic Cell Vaccines Is a Result of Their Ability to Engage Both CTL and IFN Gamma-producing NK Cells.” Molecular Therapy 16 (2): 411–418.
APA
Karimi, K., Boudreau, J. E., Fraser, K., Liu, H., Delanghe, J., Gauldie, J., Xing, Z., et al. (2008). Enhanced antitumor immunity elicited by dendritic cell vaccines is a result of their ability to engage both CTL and IFN gamma-producing NK cells. MOLECULAR THERAPY, 16(2), 411–418.
Vancouver
1.
Karimi K, Boudreau JE, Fraser K, Liu H, Delanghe J, Gauldie J, et al. Enhanced antitumor immunity elicited by dendritic cell vaccines is a result of their ability to engage both CTL and IFN gamma-producing NK cells. MOLECULAR THERAPY. NATURE P75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA: NATURE PUBLISHING GROUP; 2008;16(2):411–8.
MLA
Karimi, Khalil et al. “Enhanced Antitumor Immunity Elicited by Dendritic Cell Vaccines Is a Result of Their Ability to Engage Both CTL and IFN Gamma-producing NK Cells.” MOLECULAR THERAPY 16.2 (2008): 411–418. Print.
@article{596022,
  abstract     = {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-gamma (IFN gamma) and mediate antitumor protection. Moreover, our data showed that exogenously delivered DCs preferentially engaged the Mac-1(high)CD27(high) NK 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.},
  author       = {Karimi, Khalil and Boudreau, Jeanette E. and Fraser, Katie and Liu, Hongju and Delanghe, Jordan and Gauldie, Jack and Xing, Zhou and Bramson, Jonathan L. and Wan, Yonghong},
  issn         = {1525-0016},
  journal      = {MOLECULAR THERAPY},
  keywords     = {IN-VIVO,RECOMBINANT ADENOVIRUS,NATURAL-KILLER-CELLS,T-CELLS,TUMOR,VACCINATION,INNATE,ANTIGEN,RESPONSES,ACTIVATION},
  language     = {eng},
  number       = {2},
  pages        = {411--418},
  publisher    = {NATURE PUBLISHING GROUP},
  title        = {Enhanced antitumor immunity elicited by dendritic cell vaccines is a result of their ability to engage both CTL and IFN gamma-producing NK cells},
  url          = {http://dx.doi.org/10.1038/sj.mt.6300347},
  volume       = {16},
  year         = {2008},
}

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