Infiltration of T cells promotes the metastasis of ovarian cancer cells via the modulation of metastasis-related genes and PD-L1 expression

摘要

Due to its high ability to disseminate, ovarian cancer remains one of the largest threats to women's health, worldwide. Evidence showed that the immune cells infiltrating the tumor microenvironment are crucial in mediating metastasis. Therefore, it is necessary to understand which types of immune cells are involved in metastasis, and to determine the mechanisms by which they influence the process. By immunohistochemistry, we found that higher concentrations of intratumoral CD8(+) T cells were found to be correlated with an advanced grade and stage of ovarian cancer. Additionally, the infiltration of stromal CD8(+) T cells was also significantly higher in tissues with advanced stages and metastatic tumors. A positive correlation between the infiltration of FoxP3(+) Treg cells and histological grade was also observed, regardless of location. PD-L1 expression in metastatic tumors was also higher than that in paired primary ovarian tumors. Transwell migration and invasion assays revealed the increased migration and invasion of ovarian cancer cell lines (A2780CP and ES2) and ascites-derived ovarian cancer cells following co-culturing with CD8(+) T cells. Enhanced expression of MMP-9, uPA, VEGF, bFGF, IL-8, IL-10, and PD-L1 by cancer cells following co-culturing with CD8(+) T cells were also detected by qPCR, ELISA or flow cytometry. In conclusion, our findings suggest that the infiltrated T cells could promote the development of ovarian cancer, and provide another mechanism of immune evasion mediated by T cells.