Nanog promotes FoxP3 expression in breast cancer stem cell that can be attenuated by aspirin treatment

Cancer stem cell (CSC) hypothesis has established CSCs as the major cause of cancer metastasis. CSCs are also known to be immunologically cold as they avoid detection by immune cells or makes them inactive. CSCs employs both active and passive mechanism to suppress host immunity, where they can passively recruit immunosuppressive cells like Treg cells to dampen anti-tumor host immune response or themselves actively express immunosuppressive molecules like PD-L1, CD47, etc. To date, not much research has been conducted on how CSCs actively express these immunosuppressive molecules. Recently FoxP3 an important immunosuppressive marker was also documented to be expressed in breast cancer cells. We aimed to explore if FoxP3 was also expressed in breast CSCs and the factors responsible for FoxP3 expression in CSCs. Our study revealed that FoxP3 is highly expressed in CSCs as compared to cancer cells. Furthermore, FoxP3 was also found to positively regulate stemness and EMT genes. Importantly, the major pluripotent factor Nanog was found to bind to the FoxP3 promoter region and acts as a positive modulator of FoxP3 expression in CSCs. Stitch analysis revealed that aspirin could be repurposed to downregulate Nanog expression in CSCs. Treatment of CSC with aspirin indeed inhibited Nanog expression and its binding to the FoxP3 promoter and thereby reduced FoxP3 expression in CSCs.