ZEB1 promotes the immune escape of ovarian cancer through the MCSF-CCL18 axis.

This study aimed to determine the molecular mechanisms underlying immune escape in ovarian cancer. Samples of ovarian cancer were used to explore the regulatory pathways involved in the malignant phenotype. Tumor cell models with different levels of factor expression were constructed via transfection, and their regulation was determined through investigation of protein expressions. Moreover, our study aimed to investigate the effects of M2 polarization and TAMs aggregation on the apoptosis of CD8 + T-cells, and determine their regulatory axis. Results revealed ZEB1 may promote CCL18 expression via upregulation of MCSF concentration. Notably, high CCL18 expression levels were associated with the aggregation of M2-TAMs and the apoptosis of CD8 + T-cells. In addition, results of the present study demonstrated that the proliferation and invasion of ovarian cancer cells with high expression levels of proteins associated with ZEB1 signal pathway were increased. At the same time the growth rate of tumors in mice was reduced following ZEB1 knockdown, and the volume/weight of tumors were markedly decreased both in vitro and in vivo. Moreover, our results revealed that the aggregation of M2-TAMs and the apoptosis of CD8 + T-cells were significantly decreased in tumor cells following ZEB1 knockdown. Thus, these results verified that ZEB1 may promote the M2 polarization of TAMs via the MCSF axis, leading to the increased secretion of CCL18. Moreover, the MCSF axis may mediate immune escape through the induction of CD8 + T-cell apoptosis, ultimately promoting the malignant phenotype in ovarian cancer cells.