Evaluation of Myeloid-derived Suppressor Cells and Components of Renin Angiotensin System in Urethaneinduced Lung Cancer

Urethane-induced lung cancer has been associated with an imbalance in the effector/suppression immune response since interferon-gamma production is increased along with elevated percentages of myeloid-derived suppressor cells. The goal in cancer therapy is to prevent the immunosuppressive effects caused by tumor and thus lead to the development of effective immune response. The depletion of myeloid-derived suppressor cells in experimental models causes less tumor burden and improves the immune response but doesn´t provide cure. As cancer is a complex and multifactorial disease the treatment also should be based on multiple targets. A recently described target is the renin angiotensin system and its components (i.e. bradikynin receptors, angiotensin-converting enzyme) as they may play a role in cancer development. Therefore, our aim was to investigate the percentage of myeloid-derived suppressor cells at the tumor site and the possible correlation with bradikynin receptors and angiotensin-converting enzyme expressions in mice submitted to Urethane-induced lung cancer. BALB/c mice were either injected with myeloid-derived suppressor cells, Urethane or only followed for 120 days (control). Lung, spleen, and blood were phenotyped for myeloid-derived suppressor cells and lung tissue was evaluated for the expression of renin angiotensin system components. In tumor-bearing mice it was observed a significant increase at the percentage of myeloid-derived suppressor cells in the spleen along with angiotensinconverting enzyme increased gene and decreased protein expressions in lung. Urethane administration was crucial to lung tumor development, to the increase of peripheral myeloid-derived suppressor cells and to the changes observed in angiotensin-converting enzyme (ACE). In conclusion, tumor microenvironment seems to modulate myeloid-derived suppressor cells expansion and ACE gene and protein expressions. Myeloidderived suppressor cells and renin angiotensin system components could be potential targets for cancer diagnostics and therapy.