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

Khalil Karimi, Jeanette E. Boudreau, Katie Fraser, Hongju Liu, Jordan Delanghe, Jack Gauldie, Zhou Xing, Jonathan L. Bramson, Yonghong Wan

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

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-γ (IFNγ) and mediate antitumor protection. Moreover, our data showed that exogenously delivered DCs preferentially engaged the Mac-1highCD27high 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.

Original languageEnglish
Pages (from-to)411-418
Number of pages8
JournalMolecular Therapy
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Ontario Cancer Research Network. Y.W. is a recipient of a CIHR Scholarship. J.L.B. is supported by an Rx & D—Health Research Foundation/CIHR Career Award in Health Research. J.E.B. is supported by studentships from the National Sciences and Engineering Research Council.

ASJC Scopus Subject Areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'Enhanced antitumor immunity elicited by dendritic cell vaccines is a result of their ability to engage both CTL and IFNγ-producing NK cells'. Together they form a unique fingerprint.

Cite this