Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients

Abstract

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stages II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress ( n = 8) or with low stress ( n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels ( P = 0.013; 13 μg/dl vs. 9.74 μg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/ml vs. 97.16 pg/ml; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores ( P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, vs. 27.3% in patients with low IES scores. Additional analyzes of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC ( P = 0.064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients.