Abstract

The adaptive immune response of ovarian cancer patients has been linked to survival, and is known to be impaired in the tumor microenvironment. Little is known about relationships between biobehavioral factors such as depressed mood and anxiety and the adaptive immune response in ovarian cancer. Thirty-seven patients with epithelial ovarian cancer and 14 patients with benign ovarian neoplasms completed psychosocial questionnaires pre-surgery. Lymphocytes from peripheral blood, tumor, and ascites (fluid around the tumor), were obtained on the day of surgery. Expression of the Type-1 cytokine interferon-gamma (IFNγ), and the Type-2 cytokine interleukin-4 (IL-4) by T-helper (CD4⁺) and T-cytotoxic (CD8⁺) cells was measured under autologous tumor-stimulated, polyclonally-stimulated, or unstimulated conditions. Links with mood were examined. Among cancer patients, marked elevations in unstimulated and tumor-stimulated Type-2 responses were seen, particularly in ascites and tumor-infiltrating lymphocytes (P values < 0.01). With polyclonal stimulation, lymphocytes from all compartments expressed elevated Type-1 cytokines (P values < 0.014). Depressed and anxious mood were both associated with significantly lower ratios of polyclonally-stimulated CD4⁺ cells producing IFNγ (TH₁ cells) vs. IL-4 (TH₂ cells) in all compartments (depressed mood: P = 0.012; anxiety: P = 0.038) and depressed mood was also related to lower ratios of polyclonally-stimulated CD8⁺ cells producing IFNγ (TC₁) vs. IL-4 (TC₂) (P = 0.035). Although effects of polyclonal stimulation should be generalized with caution to the in vivo immune response, findings suggest that depressed and anxious mood are associated with greater impairment of adaptive immunity in peripheral blood and in the tumor microenvironment among ovarian cancer patients.

Keywords: Ovarian cancer; Cytokines; Depressed mood; Anxiety; Psychoneuroimmunology; T-cell response; Distress; Tumor microenvironment

Article Outline

1. Introduction

2. Materials and methods

2.1. Participants

2.1.1. Inclusion and exclusion criteria

2.1.2. Sample characteristics

2.2. Procedure

2.3. Immunologic measures

2.3.1. Intracellular cytokine stain

2.4. Psychosocial assessments

2.4.1. Distressed mood

2.4.2. Clinical and demographic information

2.5. Statistical analyses

3. Results

3.1. Patient characteristics

3.2. Comparison of T-cell cytokine producing populations in benign and ovarian cancer patients

3.3. TH₁ and TH₂ cytokine producing populations among ovarian cancer patients

3.3.1. Unstimulated cells

3.3.2. Tumor-stimulated cells

3.3.3. Polyclonal stimulation

3.4. TC₁ and TC₂ cytokine producing populations in ovarian cancer

3.4.1. Unstimulated cells

3.4.2. Tumor-stimulated cells

3.4.3. Polyclonal stimulation

3.5. Mood and cytokine expressing populations in ovarian cancer patients

4. Discussion

4.1. Associations between depressive and anxious mood and cytokine production

4.2. Limitations

5. Conclusion

Acknowledgements

Appendix A. Supplementary data

References