title: [Role of tumor-derived secretary small RNAs in EBV related lymphoma].
abstract: EB virus (EBV) is associated with heterogeneous lymphomas. In these lymphomas EBV+ lymphoma cells are embedded in non-neoplastic bystanders: B and T cells, macrophages. Without these bystander cells, the lymphoma cells are incapable of being engrafted in immunodeficient mice. In this context, the bystanders are tumor-supportive "inflammatory niche". Recently, EBV-infected cells produce exosomes that contain EBV specifically encoded miRNAs (EBV-miRNAs). Accordingly, we hypothesized that exosomal EBV-miRNAs might redirect tumor surrounding immune cells from tumor reactive into tumor-supportive "inflammatory niche". The EBV-miRNAs in the exosome secreted from EBV positive lymphoma cells significantly influenced on monocyte/macrophage Mo/Mf in inducing CD69, IL-10, and TNF, suggesting that EBV-miRNAs might polarize Mo/Mf into tumor associated Mf (TAM). EBV-miRNAs were required to develop lymphoproliferative disease (LPD) in vivo mouse model. Moreover, when Mfs were depleted by clodronate liposome, EBV positive tumor cells disappeared. These results suggest that lymphoma-derived secretary EBV-miRNAs regulate Mo/Mf to support the lymphoma survival or development. Most importantly, exosomal EBV-miRNAs derived from the lymphoma cells were transferred to Mf in human EBV+ lymphoma samples, which showed correlation with prognosis.
authors.affiliation: Tokai University the Institute of Medical Science Devision of Hematological malignancy, Tokai University School of Medicien, Internal Medicien, Hematology and Oncology.
authors.forename: Ai
authors.initials: A
authors.lastname: Kotani
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004195:Disease Models, Animal; D055354:Exosomes / Q000235:genetics* / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D006801:Humans; D037181:Lectins, C-Type; D008264:Macrophages / Q000276:immunology; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000276:immunology; D011379:Prognosis; D012367:RNA, Viral / Q000502:physiology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D035683:MicroRNAs; D012367:RNA, Viral; D000099192:CD69 Antigens