肿瘤合并贫血是影响肿瘤患者预后的重要因素，探讨肿瘤状态下贫血发生的根源具有重要科学意义。申请者基于前期发现：荷瘤机体中CD45阳性红系前体细胞（CD45+EPCs）分化阻滞导致在体内大量蓄积，是抗瘤免疫应答缺陷及贫血发生的重要因素；EPOR表达缺失，是其分化阻滞的关键。并结合初步实验数据及文献支持，提出科学假说：肿瘤微环境中TGF-β通过降解TAL1，致使EPOR表达缺失，导致CD45+EPCs分化阻滞。本项目拟进一步明确EPOR表达缺失对荷瘤机体CD45+EPCs分化阻滞的影响；深入探讨TAL1蛋白降解对EPOR缺失的作用；阐明肿瘤环境中TGF-β通过降解TAL1进而调节EPOR表达的具体机制。本项目的顺利开展，不但能深入阐明肿瘤环境对CD45+EPCs分化阻滞的影响及具体机制，也将为临床上缓解肿瘤患者贫血状态，增强免疫治疗疗效提供新思路。

Cancer related anemia is an important factor causation death of cancer patients, explore the underlying causes reason have the vital significance. Based on our previous findings, differentiation defect of CD45-positive erythroid progenitor cells (CD45+ EPCs) results in large accumulation in tumor-bearing host, which was an important factor in the occurrence of anti-tumor immune deficiencies and cancer-induced anemia. In addition, the absent expression of EPOR was the key to CD45+ EPCs differentiation blockade. Combined with preliminary results and literature support, we proposed, TGF-β, which abundantly produced in tumor microenvironment, degraded TAL1 resulted in EPOR absent, causing CD45+ EPCs differentiation blockade in tumor-bearing state. In the present, we will determine the effect of EPOR absent on differentiation defect of CD45+ EPCs, and explore the effect of TAL1 protein degradation on EPOR deficiency. Moreover, we will elucidate the specific mechanism of TGF-β regulating EPOR expression by degrading TAL1 in tumor environment. Through this project, we will not only clarify the effect and specific mechanism of tumor environment on CD45+ EPCs differentiation blockade, but also provide some clues for clinical alleviation of cancer induced anemia and enhance the efficacy of immunotherapy.