Links Between Deregulated Signaling Network And Functional Deficiency In Cancer-induced Dendritic Cells

Cancer-induced DC dysfunction plays an important role in tumor immune escape and cancer development;however,the underlying mechanisms are yet fully understood due to the lack of proper experiment models both in vivo and in vitro.Using lung cancer patients' sera,we built an in vitro model of tumor associated DCs.In this model,DCs show systematic functional deficiency,which makes it impossible for them to initiate proper immune response against tumor cells.Transcriptomics analysis of tumor associated DCs reveals that lots of their functional genes,including(?)MHC-?family,(?)IL-1 and IFN-?/?signaling molecules,(?)cytokine and chemokine profiles,etc.,change significantly when cultured in cancer environment.Furthermore,we find that the upstream canonical NF-?B and STAT3 signaling pathways are both interfered in tumor associated DCs.Taken together,these results indicate that tumor environment manipulates DCs functional deficiency by inhibiting canonical NF-?B and STAT3 signaling pathways simultaneously and lead to abnormal downstream genes' transcription.Although inflammatory response are known to activate canonical NF-?B and STAT3 signaling,these two pathways turns out to be attenuated in tumor associated DCs,and the abnormal signaling cross-talk could be the reason involved.Insights into the molecular mechanisms of tumor associated DCs may help us understand DC-dependent tumor immune escape,making it possible for us to manipulate the inhibitory signals and promote cancer immunesurveillance.