血液贮存损伤与肿瘤患者输血后相关免疫抑制、术后感染、肿瘤复发等不良预后已引起国内外学者广泛关注，其机制未明。肿瘤微环境是保护支持肿瘤进程及转移的必要元素，与肿瘤细胞相互刺激促进肿瘤发展和转移。本课题组前期研究发现储存血中泛素浓度随保存时间延长显著升高，并可与Treg细胞结合影响患者免疫抑制作用的发挥并明显促进肿瘤细胞迁移。Treg细胞作为免疫细胞的同时又是肿瘤微环境的重要组成，由其调控TGF-β/MMP-9通路在肿瘤转移过程中发挥重要作用。据此提出基于肿瘤微环境基础的储存血中泛素影响肿瘤转移的分子机制研究，拟验证1）泛素基于肿瘤微环境影响肿瘤细胞迁移;2）泛素对肿瘤微环境及TGF-β/MMP-9通路的影响;3）TGF-β/MMP-9通路影响肿瘤微环境进而调控肿瘤转移;4）泛素对肿瘤患者微环境的影响。预期结果有助于阐明输血对肿瘤转移影响的微环境机制，为有效预防肿瘤转移与复发提供重要理论依据。

Blood transfusion can induce immune suppression，tumor recurrence and postoperative infection for tumor patients．Tumor microenvironment is key regulator for tumor progression which can promote tumor development and metastasis. Our previous studies have found ubiquitin concentration increased in the plasma of whole blood during storage, which combined with Treg cells and significantly promoted tumor cell migration. Treg cells as immune cells is also an important component of the tumor microenvironment, TGFβ/MMP-9 pathway which regulated by Treg cells, play an important role in tumor metastasis. We propose ubiquitin accumulated in the blood during storage regulates tumor microenvironment to affect tumor metastasis. So the project will try to 1) ubiquitin promote tumor cells migration via regulating microenvironment 2) the effect of ubiquitin on tumor microenvironment and TGFβ/MMP-9 pathway 3) microenvironment of TGFβ/MMP-9 pathway can influence tumor microenvironment to regulate tumor metastasis 4) the effect of ubiquitin on tumor microenvironmentof patients. Expected results will help to elucidate microenvironment mechanism of blood transfusion effect on tumor metastasis, and provide experimental and theoretical basis for the effective prevention of tumor recurrence and metastasis.