Abstract # 1782 Activating the brain to fight cancer: Reward system activation attenuates tumor growth in mice

Abstract

The immune system plays a critical role in fighting cancer. Research shows that immune activity can be affected by one’s emotional state, and that patient’s mood can impact the success of cancer therapy. Although, studies primarily focused on the effects of stress on immunity, a growing body of evidence indicates that positive emotions can also affect immunity. One of the brain circuits associated with positive affect is the brain’s reward system. Here we show that activation of the brain’s reward system can stimulate the anti-tumor immune response and significantly attenuate tumor development. We used pharmacogenetics (DREADDs) to activate the dopaminergic neurons in the ventral tegmental area (VTA), the central component of the brain’s reward system. We found that repeated VTA activation in tumor-bearing mice (Lewis lung carcinoma; LLC) significantly reduced the tumor weight by 36 percent. We attribute this effect to changes in the anti-tumor immune response. Specifically, we found that VTA activation decreased the abundance and activity of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs), known to suppress anti-tumor immune response. We further demonstrate that these effects were mediated, at least in part, via the sympathetic nervous system (SNS). Taken together, our data indicates that the reward system can affect tumor progression by enhancing the anti-tumor immune response. These findings introduce a potential mechanism whereby positive emotions can impact the organism’s ability to fight cancer.