Effects of Sema3A derived from tumor cells on functions of dendritic cells / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of tumor cell-derived Sema3A on the immunological functions of murine dendritic cells (DCs).</p><p><b>METHODS</b>Lung adenocarcinoma A549 cells were transfected with small interference RNA, Si-Sema and Si-mut, and the interference efficiency was determined by real-time PCR and Western-blot. The concentrated supernatants from cultured tumor cells, Si-Sema and Si-mut-infected tumor cells were subjected to DCs respectively. The immunophenotypes of DCs were analyzed by flow cytometry, the production of IL-12P70 and the ability of DCs to stimulate DO11. 10 T cells secreting IFN-gamma and IL-2 were detected by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Knockdown with Si-Sema3A significantly decreased the secretion of Sema3A by A549 cells in comparison with the Si-mut cells. DCs exposed to supernatants from Si-Sema cells showed elevated levels of MHC, CD40 and CD80, more production of IL-12P70, and enhanced capability of activating antigen-specific T cells, as evidenced by the remarkably increased levels of IFN-gamma and IL-2.</p><p><b>CONCLUSION</b>A549 cells secrete Sema3A to inhibit the maturation and functions of DCs, which might be associated with the unidentified mechanism of immune evasion by tumor cells.</p>