胶质母细胞瘤（glioblastoma，GBM）是常见的原发性恶性脑肿瘤，其特点是病程发展快、预后差和临床治疗困难。因此，寻找新的治疗靶点，探索新的治疗方案势在必行。申请者在前期研究中发现在GBM标本中浸润了大量的巨噬细胞，而T淋巴细胞较少；CD47丰度与胶质瘤恶性分级呈正相关，并且CD47蛋白水平受EGFR/c-Src信号调节。综上推测EGFR信号通过上调CD47促进GBM细胞逃离巨噬细胞的攻击。本课题从GBM的突变特点及所处的微环境角度出发，通过体外实验、动物实验和临床资料分析，探索CD47作为GBM精准免疫治疗靶点的可行性，并明确EGFR/c-Src调控CD47表达的具体机制，论证EGFR靶向药Afatinib与CD47抗体联用能否更有效地促进巨噬细胞的吞噬作用从而提高GBM的治疗疗效。本研究将丰富人们对GBM免疫逃逸的认识，并为GBM免疫治疗提供新思路。

Glioblastoma is a common primary malignant brain tumor, which has rapid progression, terrible prognosis and poor response to clinical treatment. Therefore, it is imperative to find new therapeutic targets and explore new therapeutic regimens. Our previous study showed that numerous of macrophages were infiltrated in GBM specimens, while less T lymphocytes were found in the specimens. Moreover, CD47 abundance was positively correlated with malignant grade of gliomas, and the protein level of CD47 was regulated by EGFR/c-Src signal. Accordingly, we speculate that activation of EGFR promotes the escape of GBM cells from macrophage attack by up-regulating CD47. Based on the mutation and microenvironment of GBM, we will explore the feasibility of CD47 as a target for precise immunotherapy of GBM, clarify the specific mechanism of EGFR/c-Src regulating CD47 expression, and finally demonstrate whether the combination of EGFR inhibitor Afatinib and CD47 antibodies can more effectively strengthen the phagocytosis of macrophage and significantly improve the therapeutic efficacy of GBM. Researches mentioned above will be carried out through in vitro studies, animal experiments and clinical data analysis. Taken together, this study will enrich the understanding of GBM immune escape and provide a new method for GBM immunotherapy.