宫颈癌患者的免疫系统处于耐受状态是癌细胞逃避免疫攻击的重要原因，髓源性抑制细胞（MDSC）是近年广泛研究的具有强大免疫抑制功能的细胞群，其在人类肿瘤中的调控机制仍不甚明了。在前期研究中，我们发现宫颈癌患者体内MDSC增多，癌细胞可高表达补体分子C3，并且其活化产物C3a在宫颈癌患者外周血及肿瘤局部表达增加，而肿瘤细胞分泌的炎症因子M-CSF可促进MDSC表达C3a受体C3aR；进一步研究发现，在C3aR基因敲除的小鼠宫颈癌模型中，肿瘤生长受限，肿瘤局部MDSC浸润明显减少。因此，我们推测宫颈癌细胞可能通过C3a/C3aR信号和M-CSF协同促进MDSC免疫抑制功能，从而发生免疫逃逸。本项目拟采用基因敲除和人源化NSG小鼠宫颈癌模型等关键技术手段，从体内体外两方面验证这一新的设想，阐明C3a/C3aR信号和M-CSF在调控宫颈癌MDSC中的作用和机制，为寻找新的宫颈癌治疗的有效靶点奠定基础。

The immune system of patients with cervical cancer in a state of tolerance is an important cause of cancer cells evading immune attack. Myeloid derived suppressor cells (MDSC) with powerful immunosuppression function in human tumors is widely studied in recent years, the regulatory mechanism is still not very clear. In our previous study, we found that MDSC increased in patients with cervical cancer, cancer cells can highly express the complement molecule C3, and expression of the activation product C3a in peripheral blood and tumor location of patients with cervical cancer also increase. M-CSF, an inflammatory factors secreted by tumor cells can promote the C3a receptor C3aR expression in MDSC; Further study in C3aR gene knockout mouse model of cervical cancer found tumor growth restriction and significantly reduced MDSC infiltration of local tumor site. Therefore, we propose that cervical cancer cells may promote MDSC immune suppression function by C3a/C3aR signal cooperated with M-CSF, which occurred in immune escape. This project aims to use gene knockout and humanized NSG murine cervical carcinoma model as key technologies, to test this new idea in vivo and in vitro, and clarify mechanism of C3a/C3aR signaling plus M-CSF in MDSC regulation in cervical cancer, make the foundation for looking for new effective target of cervical cancer therapy.