The Role of Signal Transducer and Activator of Transcription protein 1 (STAT1) in a murine model of lung adenocarcinoma (ADC)

Dysregulation of cytokines and growth factors signaling can cause pathological activation of the different STATs resulting in impaired immune responses, inflammation or cancer. STAT1 plays a crucial role in tumorigenesis by controlling different functions on tumor and immune cells. In various cancer types, STAT1 induces anti-proliferative and pro-apoptotic effects, regulating the tumor growth. Previously, we found impaired levels of activated STAT1 in the tumoural region of the lung of patients, who suffered from ADC compared to their lung tumor free region. In a murine model of ADC, we confirmed these findings and found out that, Stat1 mRNA expression decreases during the tumor progress in the lung of tumor bearing mice. In STAT1KO mice we observed a significantly enhanced lung tumor development compared to controls. We detected an elevated number of macrophages associated with an increased number of positive programmed cell death protein 1+ Tregs in the lungs of tumor bearing STAT1KO mice, compared to controls. Moreover, in tumor bearing STAT1KO mice we detected decreased mRNA expression for Eomes and Perforin. Finally, loss of STAT1 leads to increased lung tumor growth favoring immunosuppressive environment and thus inhibiting the anti-tumor cytotoxic activity of tumor infiltrating immune cells.