SPOP promotes cervical cancer progress by inducing PD-1 move away from PD-L1 in spatial localization

Background: Metastasis is a major obstacle in treatment of cervical cancer (CC), and gene SPOP mediated regulatory effect is found to be involved in metastasis. However, its mechanisms have not been fully elucidated. Methods We performed proteomic sequencing, immunohistochemical staining (IHC) and scoring of SPOP in cancer tissues of 180 patients with 2009 FIGO stage IB1-IIA2 CC, and compared the expression of SPOP between pelvic lymph node (pLN) metastasis group and non-pLN metastasis group. We divided the data into two groups by SPOP expression, compared overall survival (OS) and relapse- free survival (RFS) of patients. In vitro, cells were carried out to determine whether SPOP overexpression or knockdown could affect the proliferation, cloning, wounding and Tanswell assays. Finally, the possible mechanism of pLN metastasis of CC was explored by analyzing the differences in the number and distance of various immune targets. Results SPOP is upregulated in CC with pLN metastasis and negatively associated with patient outcome. In vitro, SPOP promotes CC cell proliferation, invasion. Through further analysis, we found that there was no significant difference in the number of PD-1 and PD-L1 between the two groups, but the number of PD-1 in the range of PD-L1 100um was significantly increased. Conclusion This study presents that SPOP can inhibit the immune microenvironment by promoting PD-1 to move away from PD-L1, thereby promoting pLN metastasis of CC, resulting in worse OS and RFS in patients.