Expression of STAT1 is positively correlated with PD-L1 in human ovarian cancer

Abstract

Signal transducer and activator of transcription 1 (STAT1) is related to the immune microenvironment of tumorigenesis. The programmed cell death 1 (PD-1) and its ligand (PD-L1) have been reported to be important in immunotherapy by mediating tumor immune evasion. Blocking the PD-1/PD-L1 pathway can restore the endogenous anti-tumor immune response. This study aimed to examine the expression of STAT1, PD-1, and PD-L1 and the correlation between selected markers in human epithelial ovarian cancer (EOC). The results showed that malignant tumors contained more STAT1, PD-1, and PD-L1 positive cells. The expression of STAT1 and PD-L1 was associated with age, whereas PD-1 and PD-L1 associated with histopathological type, in patients with ovarian tumors. Moreover, the expression of STAT1 was found to be associated with disease stages and the grade of serous carcinoma. STAT1 expression was higher in OC cells than normal ovarian surface epithelial cells and was positively correlated with PD-L1 expression. The knockdown of STAT1 decreased PD-L1 expression, whereas overexpression of STAT1 increased PD-L1 expression. Furthermore, the expression of STAT1, PD-1, and PD-L1 was lower in paclitaxel-resistant cells than sensitive cells. Finally, STAT1 affected the overall survival and progression-free survival of patients with EOC. These findings suggest that STAT1, PD-1, and PD-L1 are the tissue markers of EOC and imply the possibility that the high level of STAT1, PD-1, and PD-L1 may favor the checkpoint immunotherapy in patients with EOC, but may have a limit in paclitaxel-resistant patients because of the low expression of STAT1, PD-1, and PD-L1 in paclitaxel-resistant cells.

Leveraging a necroptosis pattern to predict the prognosis and drug sensitivity of ovarian cancer

“…Novel antitumor therapies that target the PD-1 receptor and its ligands (PD-L1) can reverse cancermediated immune evasion [40]. A set of data by Liu et al [41] suggested that STAT1 and PD-L1 are overexpressed in OC and showed a positive correlation between the two, suggesting the feasibility of targeting PD-1/PD-L1 in patients with OC. Conversely, a recent study con rmed that up-regulated STAT1 induces EOC cell proliferation, migration, and invasion; whereas its inhibition suppresses the proliferation, migration, and invasion of the EOC cells.…”

The current landscape of predictive and prognostic biomarkers for immune checkpoint blockade in ovarian cancer

“…Signal transducer and activator of transcription 1 (STAT1) has been demonstrated to be associated with TME. A recent study found that STAT1 expression was positively correlated with PD-L1 expression and had the potential to predict the response to ICB in patients with EOC (24). Integrins are transmembrane receptors that mediate the connection between cells and their external environment (49)(50)(51).…”

The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials

“…Signal transducer and activator of transcription 1 is overexpressed in OC compared with normal ovarian tissue ( Tian et al, 2018 ; Liu et al, 2020 ) and is associated with the overall survival of patients ( Josahkian et al, 2018 ). High levels of STAT1 evaluated by immunohistochemistry is associated with longer overall survival and progression-free survival of patients with high-grade serous ovarian cancer (HGSOC) ( Table 1 ; Koti et al, 2015 ; Au et al, 2016 ; Josahkian et al, 2018 ).…”

“…The blockage of IDO by iNOS-induced-NO may lead to a favorable prognosis ( Munn and Mellor, 2016 ). Our previous study suggested that the elevated PD-L1 and STAT1 may favor the checkpoint immunotherapy in patients with EOC, but may have a limit in paclitaxel-resistant patients because of the low expression of PD-L1 and STAT1 ( Liu et al, 2020 ).…”