Presurgical stress management improves postoperative immune function in men with prostate cancer undergoing radical prostatectomy.

OBJECTIVE: To assess whether stress management (SM) improved immune outcomes in men undergoing surgery for prostate cancer. METHODS: A total of 159 men were assigned randomly to a two-session presurgical SM intervention, a two-session supportive attention (SA) group, or a standard care (SC) group. Men in the SM group discussed their concerns about the upcoming surgery and were taught diaphragmatic breathing, guided imagery; they had an imaginal exposure to the day of surgery and learned adaptive coping skills. Men in the SA group discussed their concerns about the upcoming surgery and had a semistructured medical interview. Blood samples were collected at baseline (1 month before surgery) and 48 hours after surgery. Measures of mood (Profile of Mood States) were collected at baseline, 1 week pre surgery, and the morning of surgery. RESULTS: Men in the SM group had significantly higher levels of natural killer cell cytotoxicity (p = .04) and higher levels of circulating proinflammatory cytokines (interleukin [IL]-12p70, p = .02; IL-1ß, p = .02; tumor necrosis factor-α, p = .05) 48 hours post surgery than men in the SA group and higher levels of natural killer cell cytotoxicity (p = 0.02) and IL-1ß (p = .05) than men in the SC group. Immune parameters increased for the SM group and decreased or stayed the same for the SA and SC groups. The SM group had significantly lower Profile of Mood States scores than the SC group (p = .006), with no other group differences between SA and SC groups. Changes in mood were not associated with immune outcomes. CONCLUSIONS: The finding that SM leads to decreased presurgical mood-disturbance and increased immune parameters after surgery reveals the potential psychological and biological benefits of presurgical SM.

A new approach for the large-scale generation of mature dendritic cells from adherent PBMC using roller bottle technology.

BACKGROUND: Human monocyte-derived DC (mDC) loaded with peptides, protein, tumor cell lysates, or tumor cell RNA, are being tested as vaccines against multiple human malignancies and viral infection with great promise. One of the factors that has limited more widespread use of these vaccines is the need to generate mDC in large scale. Current methods for the large-scale cultivation of mDC in static culture vessels are labor- and time- intensive, and also require many culture vessels. Here, we describe a new method for the large-scale generation of human mDC from human PBMC from leukopheresis or buffy coat products using roller bottles, never attempted before for mDC generation. We have tested this technology using 850 cm2 roller bottles compared to conventional T-175 flat-bottom static culture flasks. METHODS: DC were generated from adherent human PBMC from buffy coats or leukopherisis products using GM-CSF and IL-4 in T-175 static flasks or 850 cm2 roller bottles. The cells were matured over two days, harvested and analyzed for cell yield and mature DC phenotype by flow cytometry, and then functionally analyzed for their ability to activate allogeneic T-cell or recall antigen peptide-specific T-cell responses. RESULTS: Monocytes were found to adhere inside roller bottles to the same extent as in static culture flasks. The phenotype and function of the mDC harvested after maturation from both type of culture systems were similar. The yield of mDC from input PBMC in the roller bottle system was similar as in the static flask system. However, each 850 cm2 roller bottle could be seeded with 4-5 times more input PBMC and could yield 4-5 times as many mDC per culture vessel than the static flasks as a result. CONCLUSION: Our results indicate that the roller bottle technology can generate similar numbers of mDC from adherent PBMC as traditional static flask methods, but with having to use fewer culture vessels. Thus, this may be a more practical method to generate mDC in large-scale cutting down on the amount of laboratory manipulations, and can save both time and labor costs.

Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.

PURPOSE: Evidence has supported the association between psychological factors and cancer biology; however, findings are equivocal on the role of psychosocial factors in cancer progression. This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines associated activation of transcription control pathways. METHODS: Patients with metastatic RCC (n = 217) were prospectively enrolled in this study. Patients completed questionnaires (Centers for Epidemiologic Studies-Depression; SF-36 Health Status Survey; Duke Social Support Index; Coping Operations Preference Enquiry; organized and non-organized religious activity; and intrinsic religiosity), and provided blood and saliva samples. Cortisol levels and whole genome transcriptional profiling were assessed to identify potential alterations in circadian rhythms and genomic pathways. RESULTS: Separate Cox regression models, controlling for disease risk category, revealed that CES-D scores (p = 0.05, HR = 1.5, 95% CI for HR: 1.00-2.23) and cortisol slope (p = 0.002; HR = 1.9; 95%CI for HR: 1.27-2.97) were significantly associated with decreased survival. Only cortisol slope and risk category remained significant in the complete model. Functional genomic analyses linked depressive symptoms to increased expression of pro-inflammatory and pro-metastatic genes in circulating leukocytes. 116 transcripts were found to be upregulated by an average of 50% or more in high CES-D patients, and 57 transcripts downregulated by at least 50%. These changes were also found in the tumor in a subset of patients. CONCLUSION: These findings identify depressive symptoms as a key predictor of survival in renal cell carcinoma patients with potential links to dysregulation of cortisol and inflammatory biology.