肿瘤与免疫细胞互作并重塑宿主免疫系统是其发生发展的关键。迄今，对免疫细胞共同前体造血干细胞（hematopoietic stem cells，HSCs）在肿瘤免疫重编程中的作用仍不清楚。利用模型动物和癌症患者样本的初步试验表明，肿瘤环境下HSCs呈现显著活化；在小鼠，此过程伴有细胞增殖调控基因slfn2的急剧下调。为探明肿瘤诱导HSCs激活的特点、规律及分子机制，本项目以结肠癌为例，结合运用小鼠模型和临床样本，拟开展如下研究：1）检测肿瘤发生不同阶段HSCs的活化状态及重建活性；2）鉴定参与肿瘤诱导HSCs激活的细胞因子；3）剖析slfn2在HSCs激活中的作用及关联信号通路；4）通过转录组测序分析荷瘤小鼠骨髓HSCs和癌症病人外周血HSCs的基因表达特征。项目结果将为解决肿瘤免疫系统性功能障碍和免疫逃逸等重大问题提供新的理解视角，而且有可能推动基于造血干细胞干预肿瘤疗法的创建。

Reshaping the host immune system via dynamic interplay between tumor cells and immune cells is critical for tumor development and progression. However, it has remained unclear so far whether hematopoietic stem cells (HSCs), the common precursor of all immune cell types, play a role in the reprogramming of tumor immune response. Our preliminary studies with modeling animals and samples from cancer patients showed that under tumor environment HSCs, which exist predominantly in a quiescent state under physiological conditions, become activated，a process accompanied by sharp downregulation of the cell proliferation regulation gene slfn2 in mouse bone marrow HSCs. In order to shed light on the features of tumor-induced HSC activation and functional implications as well as underlying molecular mechanisms, the present project, which focuses on colon cancer and utilizes both mouse tumor model and blood samples from cancer patients, is designed to perform the following studies: 1) Determining the activation status and reconstitution capabilities of HSCs at different stages of tumor development; 2) Identifying key cytokines involved in HSC activation induced by tumor and/or inflammation; 3) Dissecting the roles of slfn2 in the regulation of HSC activation and related signaling pathways; 4) Exploring the gene expression patterns of HSCs from bone marrow of tumor-bearing mice and those from peripheral blood of cancer patients by transcriptome sequencing. The results obtained from this program will provide a new perspective for addressing important issues regarding the systematic impairment of caner immunity and tumor immunoevasion, and may also lead to development of novel cancer therapies based on hematopoietic stem cell intervention.