The Effect And Mechanism Of Anti-CD40-induced Inflammatory E-cadherin+Dendritic Cells In Immune Microenviroment Of Murine Lewis Lung Carcinoma

Background and objective Lung cancer is the most common cause of cancer-related death worldwide. Recently, surgery, radiation therapy, chemotherapy and targeted therapy as the main therapy of lung cancer.However, there is no conventional way to radical cure lung cancer. Unlike solid tumors, non small cell lung cancer are non-immunogenic tumours.In the field of cancer therapy, immunotherapy is become more and more popular. Agonistic CD40antibodies 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 CD40antibody-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-CD40model 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.Results Here, we demonstrated that anti-CD40-mediated E-cadherin+inflammatory DCs accumulate in the lungs of Rag1KO mice and were able to stimulate naive CD4+T cells to induce Thl and Th17cell differentiation and polarisation and to inhibit regulatory T cell and Th2responses. Importantly, with the adoptive transfer of E-cadherin+DCs into the Lewis lung cancer model, the inflammatory DCs increased the Thl and Th17cell responses and reduced the Treg cell and Th2responses. Interestingly, following the injection of inflammatory E-cadherin+DCs, the CEA-specific CD8+T cell (Day14, E-cad+group VS E-cad-group:2.01%VS1.31%, Day21, E-cad+groupVS E-cad-group:3.47%VS1.94%, Day28, E-cad+group VS E-cad-group:4.85%VS2.57%) and CD103+CD8+T cell (E-cad+group VS E-cad-group:15.20%VS3.70%) 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.