tailieunhanh - báo cáo hóa học:" Functional characterization of human Cd33+ And Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Functional characterization of human Cd33+ And Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines | Lechner et al. Journal of Translational Medicine 2011 9 90 http content 9 1 90 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Functional characterization of human Cd33 And Cd11b myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines Melissa G Lechner Carolina Megiel Sarah M Russell Brigid Bingham Nicholas Arger Tammy Woo and Alan L Epstein Abstract Background Tumor immune tolerance can derive from the recruitment of suppressor cell populations including myeloid-derived suppressor cells MDSC . In cancer patients MDSC accumulation correlates with increased tumor burden but the mechanisms of MDSC induction remain poorly understood. Methods This study examined the ability of human tumor cell lines to induce MDSC from healthy donor PBMC using in vitro co-culture methods. These human MDSC were then characterized for morphology phenotype gene expression and function. Results Of over 100 tumor cell lines examined 45 generated canonical CD33 HLA-DRlowLineage- MDSC with high frequency of induction by cervical ovarian colorectal renal cell and head and neck carcinoma cell lines. CD33 MDSC could be induced by cancer cell lines from all tumor types with the notable exception of those derived from breast cancer 0 9 regardless of hormone and HER2 status . Upon further examination these and others with infrequent CD33 MDSC generation were found to induce a second subset characterized as CD11b CD33lowHLA-DRlowLineage-. Gene and protein expression antibody neutralization and cytokine-induction studies determined that the induction of CD33 MDSC depended upon over-expression of IL-1p IL-6 TNFa VEGF and GM-CSF while CD11b MDSC induction correlated with over-expression of FLT3L and TGFp. Morphologically both CD33 and CD11b MDSC subsets appeared as immature myeloid cells and had significantly up-regulated expression of iNOS NADPH oxidase and arginase-1 genes. .