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，其在宫颈癌中的调控机制仍不甚明了。我们前期通过表达谱芯片筛选并验证了趋化素样因子4(CMTM4)在宫颈癌组织中的表达显著增加，而宫颈癌患者体内MDSC也显著增多；进一步研究发现，用CMTM4基因敲低的小鼠宫颈癌细胞株TC-1构建肿瘤模型，结果显示肿瘤局部MDSC浸润明显减少，其分泌的免疫抑制因子Arg1减少，肿瘤生长受限。因此，我们推测CMTM4分子可能在宫颈癌促进MDSC免疫抑制功能，发生免疫逃逸的过程中发挥重要作用，这不同于以往关于CMTM4可能是抑癌基因的报道。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CMTM4信号在宫颈癌调控MDSC中的作用和机制，为寻找新的宫颈癌治疗靶点奠定基础。

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 are widely studied in recent years, but the regulatory mechanism is still not very clear in cervical cancer. In our previous study, we found that the amount of MDSC increased in patients with cervical cancer, and cancer tissue could highly express the CKLF-like MARVEL transmembrane domain containing family member 4 by expression microarray screening. Further study in mouse model which was constructed by CMTM4 gene knockdown TC-1 cervical cancer cell, found tumor growth restriction, significantly reduced MDSC function and infiltration of local tumor site. Therefore, we propose that cervical cancer cells may promote MDSC immune suppression function by CMTM4 signal, which occurred in immune escape. This is different from the previous reports that CMTM4 might be a tumor suppressor gene. 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 CMTM4 signaling in MDSC regulation in cervical cancer, which will make the foundation for looking for new effective target of cervical cancer therapy.