Anti-CD40-induced inflammatory E-cadherin+ dendritic cells enhance T cell responses and antitumour immunity in murine Lewis lung carcinoma

Background: agonistic cd40 antibodies have been demonstrated to activate antigen-presenting cells (apcs) and enhance antitumour t cell responses,thereby providing a new therapeutic option in cancer immunotherapy. in agonistic cd40 antibody-mediated inflammatory responses,a novel subset of e-cadherin + dendritic cells (dcs) has been identified,and little is known about the role of these dcs in tumour immunity. this study investigated the effect of anti-cd40-mediated inflammatory e-cadherin + dcs in murine lewis lung carcinoma (llc). methods: the phenotype and characteristics of anti-cd40-mediated inflammatory e-cadherin + dcs isolated from the anti-cd40 model were assessed in vitro. the antitumour activity of e-cadherin + dcs were evaluated in vivo by promoting the differentiation of effector cd4+ t cells,cea-specific cd8+ t cells and cd103+ cd8+ t cells and assessing their resistance to tumour challenge,including variations in tumour volume and survival curves. results: here,we demonstrated that anti-cd40-mediated e-cadherin + inflammatory dcs accumulate in the lungs of rag1 ko mice and were able to stimulate naïve cd4+t cells to induce th1 and th17cell differentiation and polarisation and to inhibit regulatory t cell and th2 responses. importantly,with the adoptive transfer of e-cadherin + dcs into the lewis lung cancer model,the inflammatory dcs increased the th1 and th17 cel responses and reduced the treg cell and th2 responses. interestingly,following the injection of inflammatory e-cadherin + dcs,the cd103+ cd8+ t cell and cea-specific cd8+ t cell responses increased and exhibited potent antitumour immunity. conclusions: these findings indicate that anti-cd40-induced e-cadherin + dcs enhance t cell responses and antitumour activity in non-small cell lung cancer (nsclc)-bearing mice and may be used to enhance the efficacy of dc-based peptide vaccines against nsclc. © 2015 zhang et al.; licensee biomed central.