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Báo cáo hóa học: " Molecular signatures of maturing dendritic cells: implications for testing the quality of dendritic cell therapies"

Molecular signatures of maturing dendritic cells: implications for testing the quality of dendritic cell therapies | Jin et al. Journal of Translational Medicine 2010 8 4 http www.translational-medicine.eom content 8 1 4 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Molecular signatures of maturing dendritic cells implications for testing the quality of dendritic cell therapies Ping J li 1 Tae Hee Han1 2t Jiaqiang Ren1 Stefanie Saunders1 Ena Wang1 Francesco M Marincola1 David F Stroncek1 Abstract Background Dendritic cells DCs are often produced by granulocyte-macrophage colony-stimulating factor GM-CSF and interleukin-4 IL-4 stimulation of monocytes. To improve the effectiveness of DC adoptive immune cancer therapy many different agents have been used to mature DCs. We analyzed the kinetics of DC maturation by lipopolysaccharide LPS and interferon-y IFN-y induction in order to characterize the usefulness of mature DCs mDCs for immune therapy and to identify biomarkers for assessing the quality of mDCs. Methods Peripheral blood mononuclear cells were collected from 6 healthy subjects by apheresis monocytes were isolated by elutriation and immature DCs iDCs were produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 4 8 and 24 hours in culture with LPS and IFN-y and were then assessed by flow cytometry ELISA and global gene and microRNA miRNA expression analysis. Results After 24 hours of LPS and IFN-y stimulation DC surface expression of CD80 CD83 CD86 and HLA Class II antigens were up-regulated. Th1 attractant genes such as CXCL9 CXCL10 CXCL11 and CCL5 were up-regulated during maturation but not Treg attractants such as CCL22 and CXCL12. The expression of classical mDC biomarker genes CD83 CCR7 CCL5 CCL8 SOD2 MT2A OASL GBP1 and HES4 were up-regulated throughout maturation while MTIB MTIE MTIG MTIH GADD45A and LAMP3 were only up-regulated late in maturation. The expression of miR-155 was up-regulated 8-fold in mDCs. Conclusion DCs matured with LPS and IFN-y were characterized by increased levels of Th1 attractants as opposed to Treg attractants .