Proteomic and miRnome analysis of exosome in Sezary syndrome

Abstract

The cutaneous T-cell lymphoma (LCCT), non-Hodgkin type, includes one of the most aggressive forms the Sézary syndrome (SS). The malignant cells are the lymphocyte TCD4+, present in the peripheral circulation, skin, lymph nodes and, in some cases, viscera. Due to tumor escape mechanisms occurs immunity decline, including crucial components of the antitumor response and for the control of disease progression. Intercellular communication is performed by soluble factors or by secreted extracellular vesicles called exosomes. These vesicles display broad immunomodulatory action due to the presence of cytokines, chemokines, tetraspanins, ligands of activation or inhibition receptors as well as microRNAs. MicroRNAs are regulators of immune response able to affect maturation, proliferation, differentiation and activation of immune cells, as well as antibodies production and secretion of inflammatory mediators. Therefore, the objective of this work is to analyze the proteomic profile of extracellular vesicles from plasma and microRNAs derived from CD4+ T cells of patients with SS. The ability of the extracellular vesicles to induce suppression/activation will be analysed in T cells from healthy individuals. For this purpose, the extracellular vesicles will be assessed from plasma and from peripheral blood CD4+ T cells cultures from SS patients and healthy individuals. Extracellular vesicles derived from TCD4+ cells will be profiled for miRNA expression by microarray and for the ability to induce activation or inhibition of T cells from healthy individuals. Characterization of extracellular vesicles from both, plasma and T-cells, analyzing their functional analysis in cellular systems will be crucial for a better understanding of the immunopathogenesis of the disease as well as to obtain new biomarkers for SS. (AU)