The role of WWOX protein in tumor immunity

WWOX protein expression is often lost or reduced in most human cancers. Loss of Wwox protein expression is common in triple negative breast cancers. The immune system plays an active role in the development, progression and control of breast cancer. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint molecule involved in escape from the immune system. PD-L1 is expressed in a variety of immune cells and many different tumor types, including breast cancer. STAT3 plays an important role in the regulation of PD-L1 expression. PD-L1 is overexpressed in breast cancer cell lines due to JAK-mediated STAT3 phosphorylation and activation. The STAT3 signaling pathway is activated as an atypical signal transmitter of IFN-γ in cancer cells. WWOX suppresses growth and metastasis of cancer cells through the IL-6 / JAK2 / STAT3 signal transduction pathway, depending on STAT3. Overexpression of WWOX inhibits STAT3 activity in basal breast cancer cells. All these findings suggest that WWOX can play a possible role in the regulation of PD-L1 expression and thus act as a potential suppressor in the progression and metastasis of breast cancer. The aim of this thes is to investigate the effects of WWOX on PD-L1 expression at basal level and / or IFN-γ stimulated in MDA-MB-231 human triple negative breast cancer cells. Transient transfections were performed to overexpress WWOX in MDA-MB-231 cells. Overexpression of the WWOX protein was assessed by western blotting. PD-L1 expression was analyzed by flow cytometry system. A statistically significant increase in expression of PD-L1 was found in cells expressing WWOX compared to cells not expressing WWOX (p=0.05). In addition to these findings, a statistically significant increase in expression of PD-L1 was found in cells expressing WWOX in IFN-γ treated cells compared to cells not expressing WWOX (p=0.05). As a result, the increase of WWOX expression in MDA-MB-231 cells significantly decreased PD-L1 expression levels in the presence or absence of IFN-γ compared to MDA-MB-231 cells not expressing WWOX.