Brain, Behavior, and Immunity

The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients

Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. Greater hope was significantly related to a steeper cortisol slope, β = -0.193, p = 0.046, and lower night cortisol, β = -0.227, p = 0.018, plasma IL-6, β = -0.142, p = 0.033, and ascites IL-6, β = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol β = -0.233,p = 0.017 and ascites IL-6, β = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, β = 0.211, p = 0.031. These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.

The relationship of lifetime history of depression on the ovarian tumor immune microenvironment

Depression is associated with a higher ovarian cancer risk. Prior work suggests that depression can lead to systemic immune suppression, which could potentially alter the anti-tumor immune response. We evaluated the association of pre-diagnosis depression with features of the anti-tumor immune response, including T and B cells and immunoglobulins, among women with ovarian tumor tissue collected in three studies, the Nurses' Health Study (NHS; n = 237), NHSII (n = 137) and New England Case-Control Study (NECC; n = 215). Women reporting depressive symptoms above a clinically relevant cut-point, antidepressant use, or physician diagnosis of depression at any time prior to diagnosis of ovarian cancer were considered to have pre-diagnosis depression. Multiplex immunofluorescence was performed on tumor tissue microarrays to measure immune cell infiltration. In pooled analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the positivity of tumor immune cells using a beta-binomial model comparing those with and without depression. We used Bonferroni corrections to adjust for multiple comparisons. We observed no statistically significant association between depression status and any immune markers at the Bonferroni corrected p-value of 0.0045; however, several immune markers were significant at a nominal p-value of 0.05. Specifically, there were increased odds of having recently activated cytotoxic (CD3 Our results provide suggestive evidence that depression may influence ovarian cancer outcomes through changes in the tumor immune microenvironment, including increasing T cell activation and exhaustion and reducing antibody-producing B cells. Further studies with clinical measures of depression and larger samples are needed to confirm these results.