MiR21 sensitized B-lymphoma cells to ABT-199 via ICOS/ICOSL-mediated interaction of Treg cells with endothelial cells

摘要: MicroRNAs (miRs) are involved in tumor progression by regulating cells and microenvironment. MiR21 is overexpressed diffuse large B-cell lymphoma (DLBCL) its biological impact on microenvironment remains unclear. was assessed quantitative RT-PCR patients with newly diagnosed DLBCL. The mechanism of action miR21 angiogenesis examined vitro B-lymphoma cell lines vivo a murine xenograft model. Serum significantly elevated associated advanced disease stage, International Prognostic Index indicating intermediate-high high-risk, increased angiogenesis. When co-cultured immune endothelial cells, miR21-overexpressing were resistant to chemotherapeutic agents, but sensitive Bcl-2 inhibitor ABT-199, irrespective expression cells. In both co-culture systems Bcl-2positive Bcl-2negative induced inducible co-stimulator (ICOS) regulatory T (Treg) Through crosstalking Treg ICOS ligand (ICOSL), activated, resulting stimulation vessel formation. ABT-199 directly targeted apoptosis inhibited model established subcutaneous injection particularly retarded the growth tumors, consistent induction inhibition As serum oncogenic biomarker lymphoma, indicated sensitivity via ICOS/ICOSL-mediated interaction