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Cross‐Talk Between NK Cells and Adenovirally‐Engineered Dendritic Cell Vaccines
Author(s) -
Vujanovic Lazar,
Newton Sarah,
Landsberg Jennifer C.,
Vujanovic Nikola L.,
Butterfield Lisa H.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1079.26
Subject(s) - granzyme b , granzyme , cytotoxic t cell , cd16 , interleukin 12 , il 2 receptor , interleukin 21 , antigen presenting cell , dendritic cell , biology , antigen , nk 92 , elispot , immunology , microbiology and biotechnology , perforin , immune system , t cell , cd3 , in vitro , cd8 , biochemistry
Recombinant adenoviral vectors (AdV) are an effective modality for antigen engineering of dendritic cells (DC) in order to harness DC immunostimulatory ability and activate tumor antigen‐specific T cells. Little is known about the capacity of AdV‐transduced DC (AdV/DC) to activate natural killer (NK) cells, and stimulate their cytotoxic and regulatory abilities. Here, we have investigated the effects of AdV transduction on the ability of DC to activate, and become activated by NK cells. We showed that AdV transduction does not enhance DC sensitivity to Granzyme B‐mediated lysis by NK cells when compared to immature DC (iDC). AdV/DC and matured DC both enhance activation of CD56 hi CD16 − and CD56 dim CD16 + NK cell subsets, based on the expression of Granzyme B, CD25, and CD69 activation markers. We detected this effect in short and long‐term cultures, as well as in clinical trial patient PBMC samples post‐AdV/DC vaccination. Reciprocally, NK cells enhance the state of AdV/DC maturation in short‐term co‐cultures according to surface marker expression and cytokine profile evaluation. Moreover, NK cells pre‐activated with AdV/DC kill K562 tumor cells more efficiently than those from iDC co‐culture by Granzyme B ELISPOT. Together, this data demonstrates that there is a positive cross‐talk between AdV/DC and NK cells, which may be an additional pathway by which this vaccine platform may induce anti‐tumor activity. This work was supported by the University of Pittsburgh Cancer Institute and the Henry L. Hillman Foundation (to L.H.B.)