Abstract
Background:Triple-negative breast cancer constitutes approximately 15-20% of breast cancers and continues to be challenging to treat despite significant therapeutic advances. Epidemiological evidence suggests psychological stress correlates with decreased survival rates, while physical activity is presumed to improve survival rates of breast cancer patients. These correlations lead us to inquire whether aerobic exercise could improve cancer outcomes despite the psychological stress associated with a cancer diagnosis. In part, these parallels may be mediated by alterations in the anti-tumor immune responses meditated by neuroendocrine changes experienced during stress, which are believed to affect cancer progression. To address this, we used a syngenetic mouse model of breast cancer to study the impact of stressors.
Objective: This study investigated the effects of psychological stress and/or physical activity on tumor growth and cancer immunity in mice with murine triple-negative breast cancer.
Methods: We used female BALB/c mice subcutaneously injected with murine EMT6 breast carcinoma cells. Mice were assigned to treatment groups: moderate aerobic exercise, unpredictable chronic mild stress, a combination of exercise and chronic stress, or no physical/psychological stressor.
Results: Mice were assessed for tumor growth and immunological changes within the primary tumors. Our studies showed both aerobic exercise and chronic mild stress resulted in larger tumors, while non-stressed/non-exercised controls had consistently smaller tumors. We found the smaller tumors exhibited higher presence of T helper and cytotoxic T cells. Additionally, we demonstrated that exercise improves the proliferative and suppressive functions of T helper and T regulatory cells, respectively, whether with or without chronic stress. Interestingly, the anti-tumor cytotoxic T cell function was enhanced in exercised mice, but these functional benefits were not observed when chronic stress was added. Notably, the decreased cytotoxicity results are correlated with increased PD-1 expression.
Conclusions: Neither physical activity nor psychological stress reduced tumor growth once established; instead, they significantly increased tumor progression. Exercise did not appear to mitigate the impact of psychological stress on tumor growth or combat the negative impacts on anti-tumor immunity. However, our findings did suggest different stressors impact key anti-tumor immune cell numbers and functions that will need to be considered when developing treatment plans.