Impact of physical and psychological stressors on tumor growth and immune responses in breast cancer.

Background: Epidemiological studies suggest that heightened psychological stress is associated with poor breast cancer outcomes, while regular physical activity is presumed to improve patient prognosis. These correlations raise the question of whether aerobic exercise might offset the detrimental effects of psychological stress on cancer progression. Neuroendocrine changes during stress are believed to alter anti-tumor immune responses, potentially influencing cancer outcomes. Objective: This study investigated the impact of psychological stress and/or aerobic exercise on tumor growth and anti-tumor immunity in a syngeneic mouse model of breast cancer. Methods: Female BALB/c mice were subcutaneously injected with EMT6 breast carcinoma cells and assigned to one of four treatment groups: moderate aerobic exercise (Ex), unpredictable chronic mild stress (UCMS), a combination of both (UCMS-Ex), or untreated controls. At study completion, tumor size and immune profiles were assessed. Results: Tumors were consistently smaller in non-stressed, non-exercised control mice, while both aerobic exercise and chronic mild stress, individually or combined, led to larger tumors. Smaller tumors were associated with increased infiltration of T helper and cytotoxic T cells. Exercise enhanced the proliferative capacity of T helper cells and the suppressive function of regulatory T cells, regardless of chronic stress exposure. Although aerobic exercise alone improved cytotoxic T cell activity, this anti-tumor function was diminished when chronic stress was present. Conclusions: In summary, neither physical activity nor psychological stress reduced tumor growth once tumors were established; instead, both accelerated tumor progression. While exercise alone enhanced EMT6-specific cytotoxic T cell function, this benefit was lost in the presence of chronic stress. Exercise did not mitigate the tumor-promoting effects of stress or restore impaired anti-tumor immunity. However, our findings in sedentary mice with smaller tumors reinforce the established association between increased intra-tumoral T cell presence and reduced tumor growth.