Dendritic cell regulation of NK‐cell responses involves lymphotoxin‐α, IL‐12, and TGF‐β

摘要: Dendritic cell (DC) vaccines induce T-cell responses in cancer patients. However, there is a paucity of data regarding the role DC shaping natural killer (NK) responses. Here, we observe that NK cells are less activated following vaccination. In vitro, DC-mediated inhibition did not require cell-to-cell contact, but required increased Signal transducer and activator transcription 3 (STAT3) phosphorylation (pSTAT3) DCs. When STAT3 was inhibited DCs, found DCs suppress cells, observed an increase production lymphotoxin-alpha (LTα) interleukin-12 (IL-12) as well reduced release transforming growth factor beta (TGF-β). The addition recombinant LTα or IL-12 to DC-NK-cell cocultures restored NK-cell activity, neutralization TGF-β resulted elevated from Compared with LPS, matured cocktail R848, poly I:C, IFN-γ showed levels pSTAT3 higher inhibit activity. These results show LTα, IL-12, involved cross-talk between Our findings have important implications for development DC-based vaccination strategies potentiate patients cancer.