4.5 Article

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

Journal

CELLULAR IMMUNOLOGY
Volume 270, Issue 1, Pages 80-87

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2011.04.003

Keywords

Stress; Myeloid-derived suppressor cells; MDSC; Pro-inflammatory cytokines

Funding

  1. National Institutes of Health (NIH) [T32 GM068412, P01 CA95426, K24 CA93670, R01 MH51487]
  2. American Cancer Society [PBR-89, RSGPB-03-248-01-PBP, PF-07-169-01-CPPB]
  3. Longaberger Company-American Cancer Society [PBR-89A]
  4. US Army Medical Research [DAMD17-94-J-4165, DAMD17-96-1-6294, DAMD17-97-1-7062]
  5. National Cancer Institute [K05 CA098133, R01 CA92704]
  6. General Clinical Research Center [M01-RR0034]
  7. Ohio State University Comprehensive Cancer Center [P30 CA16058]
  8. NATIONAL CANCER INSTITUTE [P30CA016058, R01CA092704, K24CA093670, K05CA098133, P01CA095426] Funding Source: NIH RePORTER
  9. NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000034] Funding Source: NIH RePORTER
  10. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM068412] Funding Source: NIH RePORTER
  11. NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH051487] Funding Source: NIH RePORTER

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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 mu g/dl vs. 9.74 mu g/dl). Levels of IL-1R alpha 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. (C) 2011 Elsevier Inc. All rights reserved.

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