Il-18-based combinatorial adjuvants promote the intranodal production of ccl19 by nk cells and dendritic cells of cancer patients
OncoImmunology, ISSN: 2162-4011, Vol: 2, Issue: 9, Page: e26245
2013
- 23Citations
- 20Captures
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- Citations23
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- 23
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- 20
Article Description
The effective accumulation and interaction of mature dendritic cells (DCs) and naïve T cells within lymph nodes (LNs), which are driven by the CCR 7-CC L19/CC L21 chemokine axis, are critical for the induction of adaptive T-cell immunity. Human natural killer (NK) cells activated by interleukin (IL)-18 exhibit a unique 'helper' activity in promoting productive DC-T cell interactions, inducing DC maturation and shifting DC-primed T-cell responses toward a T1 polarization. Here, we demonstrate that such IL-18-activated 'helper' NK cells uniquely stimulate DCs to produce high levels of CC L19 through tumor necrosis factor α (TNFα) and interferon γ (IFNγ), a process that relies on secondary NK-cell activation by additional inflammatory signals including IFNα, IL-15, IL-12 and IL-2. DCs activated by helper NK cells not only promote the efficient CCR 7-mediated recruitment of naïve CD8 T cells, but also stimulate their expansion and expression of granzyme B. Using an ex vivo explant culture system based on LNs isolated from colorectal cancer patients, we found that CC L19 is upregulated in human tumor-associated lymphoid tissues treated with helper NK cell-stimulating factors. Our findings demonstrate the ability of 2 signal-activated helper NK cells to promote the production of the DC- and naïve/memory T cell-attracting chemokine CC L19 in LNs, and provide a rationale for the therapeutic application of IL-18-containing 'combinatorial adjuvants' to facilitate the induction of antitumor immune responses © 2013 Landes Bioscience.
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