Exosome负载的分子信息在淋巴瘤侵袭与进展恶性生物学行为中的机制研究

本课题以淋巴瘤细胞系、骨髓基质细胞、外周血/扁桃腺单个核细胞、小鼠模型、淋巴瘤患者为研究对象，经体外体内试验系统研究淋巴瘤Exosome的生物学特性并获取Exosome传递负载分子信息致淋巴瘤侵袭与进展的直接证据，阐明Exosome参与淋巴瘤恶性特征的远处传播与肿瘤微环境之间的交流及表型转化的生物效应模式以及相关分子机制；Exosome影响淋巴瘤干细胞等异质性因素在耐药机制包括化疗药耐受与利妥昔单抗耐受中的作用及相应干预策略；发掘与淋巴瘤发生发展、增殖耐药、进展复发等恶性生物学行为相关的循环血清Exosome标志物，用于早期诊断、疗效评估、预后判断及随访监测。对淋巴瘤Exosome生物学效应的全面了解将有助于理解淋巴瘤发病机制并解决诊断、治疗、随访中涉及的实际问题，具有较大的临床应用价值。

In this study, we intend to fully investigate the biological characteristics of lymphoma exosomes in vitro and in vivo using lymphoma cell lines, bone marrow stromal cells, mononuclear cells isolated from peripheral blood/tonsil, mouse strains and lymphoma patients as models, and obtain evidence of direct causal relationship between the transfer of exosomal cargo and the invasion/progression of lymphoma. Further steps are designed to clarify the involvement of exosome in the remote transmission of lymphoma's malignant features and the intercellular communications with the tumor microenvironment resulting in the phenotype exchange, understanding the bio-effect pattern as well as the corresponding molecular mechanisms; to elucidate the interference of exosome with potential heterogeneity factors e.g. lymphoma stem cells causing drug resistance to conventional chemotherapy or even Rituximab, and the rescue strategies; to identify circulating exosomal biomarkers related to the development, proliferation, drug resistance, progression and relapse of lymphoma that can be used for early diagnosis, response evaluation, prognosis prediction and follow-up monitoring. A complete comprehensive knowledge of characteristics of lymphoma exosome would help better understand the pathogenesis of lymphoma and resolve practical problems regarding to diagnosis, treatment, and follow-up, thus provide great values in clinical application.