Stress, immunity, and cervical cancer: Psychoneuroimmunologic (PNI) results of a randomized telephone counseling intervention

8585 Background: The association between counseling benefit and improved cancer patient survival is controversial. If such an association exists, it requires biological control of tumor growth, with the immune system as the most likely effector arm. It is widely held that for anti-tumor immunity a T helper type 1 (Th1) immune response is more advantageous, by supporting antigen-specific cytotoxicity, than a T helper type 2 (Th2). The purpose of this study was to test potential QOL, neuroendocrine and immune benefits obtained from psychosocial telephone counseling (PTC). Methods: Fifty cervical cancer patients were randomized to PTC or usual care. QOL and biological specimens were collected at baseline (3–15 months post diagnosis), and four months post-enrollment, Time 2. QOL was assessed by the FACT-Cx. Saliva was collected for the evaluation of cortisol and DHEA. Blood was collected for evaluation of selected neuroendocrine and immune parameters. We defined a Th1:Th2 ratio based upon cytokine precursor frequency determined from ELISpot assays for interferon (IFN) gamma and interleukin-(IL-) 5 performed using anti-CD3 and anti-CD28 lymphocyte stimulation. Results: We demonstrated a significant improvement in overall QOL from baseline to Time 2 for PTC participants compared to the control population (absolute difference 8.15, p=0.05). We observed longitudinal changes, up to 15 fold, in the Th1:Th2 ratio. Improvement in QOL was significantly associated with an increased Th1 immune system bias and conversely a decline in QOL with a more pronounced Th2 bias, p= 0.0097 two tailed Fisher’s exact T test and Spearman Correlation Coefficient r= 0.6368 (p= 0.0002, two tailed). Evaluation of association between QOL and the neuroendocrine parameters, salivary cortisol and DHEA, demonstrated the predicted trends, but did not reach statistical significance. Conclusions: PTC can improve QOL for cervical cancer survivors. Importantly, we have shown for the first time that changes in QOL are significantly associated with a shift of immune system Th1:Th2 stance. This provides support for a biobehavioral model, which identifies potential mechanisms by which interventions that lead to improvement in QOL could also result in improved clinical outcomes. No significant financial relationships to disclose.

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Psychosocial Telephone Counseling for Survivors of Cervical Cancer: Results of a Randomized Biobehavioral Trial

Journal of Clinical Oncology ◽

10.1200/jco.2014.57.4079 ◽

2015 ◽

Vol 33 (10) ◽

pp. 1171-1179 ◽

Cited By ~ 19

Author(s):

Lari Wenzel ◽

Kathryn Osann ◽

Susie Hsieh ◽

Jo A. Tucker ◽

Bradley J. Monk ◽

...

Keyword(s):

Cervical Cancer ◽

Repeated Measures ◽

Statistical Significance ◽

Multivariable Analysis ◽

Telephone Counseling ◽

Longitudinal Change ◽

Categorical Variables ◽

Patient Reported ◽

Cytokine Levels ◽

Cancer Experience

Purpose Survivors of cervical cancer experience quality-of-life (QOL) disruptions that persist years after treatment. This study examines the effect of a psychosocial telephone counseling (PTC) intervention on QOL domains and associations with biomarkers. Patients and Methods We conducted a randomized clinical trial in survivors of cervical cancer, who were ≥ 9 and less than 30 months from diagnosis (n = 204), to compare PTC to usual care (UC). PTC included five weekly sessions and a 1-month booster. Patient-reported outcomes (PROs) and biospecimens were collected at baseline and 4 and 9 months after enrollment. Changes in PROs over time and associations with longitudinal change in cytokines as categorical variables were analyzed using multivariable analysis of variance for repeated measures. Results Participant mean age was 43 years; 40% of women were Hispanic, and 51% were non-Hispanic white. Adjusting for age and baseline scores, participants receiving PTC had significantly improved depression and improved gynecologic and cancer-specific concerns at 4 months compared with UC participants (all P < .05); significant differences in gynecologic and cancer-specific concerns (P < .05) were sustained at 9 months. Longitudinal change in overall QOL and anxiety did not reach statistical significance. Participants with decreasing interleukin (IL) -4, IL-5, IL-10, and IL-13 had significantly greater improvement in QOL than those with increasing cytokine levels. Conclusion This trial confirms that PTC benefits mood and QOL cancer-specific and gynecologic concerns for a multiethnic underserved population of survivors of cancer. The improvement in PROs with decreases in T-helper type 2 and counter-regulatory cytokines supports a potential biobehavioral pathway relevant to cancer survivorship.

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Alpha-Synuclein Induced Immune Cells Activation and Associated Therapy in Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.769506 ◽

2021 ◽

Vol 13 ◽

Author(s):

Ruichen Su ◽

Tian Zhou

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Immune System ◽

Immune Cells ◽

Neurodegenerative Disorder ◽

Alpha Synuclein ◽

Autoimmune Response ◽

T Helper ◽

Helper Type

Parkinson’s disease (PD) is a neurodegenerative disorder closely related to immunity. An important aspect of the pathogenesis of PD is the interaction between α-synuclein and a series of immune cells. Studies have shown that accumulation of α-synuclein can induce an autoimmune response that accelerates the progression of PD. This study discusses the mechanisms underlying the interaction between α-synuclein and the immune system. During the development of PD, abnormally accumulated α-synuclein becomes an autoimmune antigen that binds to Toll-like receptors (TLRs) that activate microglia, which differentiate into the microglia type 1 (M1) subtype. The microglia activate intracellular inflammatory pathways, induce the release of proinflammatory cytokines, and promote the differentiation of cluster of differentiation 4 + (CD4 +) T cells into proinflammatory T helper type 1 (Th1) and T helper type 17 (Th17) subtypes. Given the important role of α-synuclein in the immune system of the patients with PD, identifying potential targets of immunotherapy related to α-synuclein is critical for slowing disease progression. An enhanced understanding of immune-associated mechanisms in PD can guide the development of associated therapeutic strategies in the future.

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Predictors of significant emotional distress in cervical cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.6632 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 6632-6632

Author(s):

Kathryn Osann ◽

Susie Hsieh ◽

Edward L. Nelson ◽

David Cella ◽

Lari B. Wenzel

Keyword(s):

Cervical Cancer ◽

Cancer Patients ◽

Emotional Distress ◽

Telephone Counseling ◽

Depression And Anxiety ◽

Logistic Regression Models ◽

Counseling Intervention ◽

Trial Outcome Index ◽

Significant Depression ◽

Outcome Index

6632 Background: Cervical cancer patients experience serious quality of life (QOL) disruptions, which may include persistent emotional distress. Predictors of persistent or significant depression and anxiety are examined in this study. Methods: A randomized trial tested the efficacy of a psychosocial telephone counseling intervention designed to improve QOL and decrease emotional distress.The FACT-Cx Trial Outcome Index (FACT-Cx-TOI), depression and anxiety (PROMIS short forms) were collected at baseline (T1), 4 months (T2) and 9 months (T3) post enrollment. Multivariate linear and logistic regression models were used to identify predictors of distress at follow-up. Tested predictors included demographic information, stage, treatment assignment, and baseline FACT-Cx TOI and PROMIS scores. Results: 115 women were randomized to PTC and 89 to usual care, with 82% compliance for T2 and 75% at T3. PTC patients experienced a significantly greater reduction in depression from T1 to T2 compared to UC (p=0.014). At baseline, 45% of participants reported depression T-scores above 55 (0.5 SD above the US general population average), and 26% reported levels greater than 60 (>1 SD worse than average). PTC patients were significantly less likely to have depression scores >55 at T2, and significantly more likely to improve by ≥5 points at T2 after adjusting for baseline and disease characteristics. Participation in PTC, higher baseline depression and higher baseline TOI were significant independent predictors of improvement in depression from T1 to T2. Conclusions: Early identification of patients with poor QOL and significant depression can inform supportive care interventions, with potential to improve health outcomes. Funding Source: NCI R01 CA118136-01. Clinical trial information: NCT00496106.

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Increase of human papillomavirus-16 E7-specific T helper type 1 response in peripheral blood of cervical cancer patients after radiotherapy

Immunology ◽

10.1111/j.1365-2567.2008.02912.x ◽

2009 ◽

Vol 126 (4) ◽

pp. 523-534 ◽

Cited By ~ 9

Author(s):

Félix Giovanni Delgado ◽

Elizabeth Martínez ◽

María Angélica Céspedes ◽

María Mercedes Bravo ◽

María Cristina Navas ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Patients ◽

Peripheral Blood ◽

T Helper ◽

Human Papillomavirus 16 ◽

Helper Type

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Immunomodulatory effects of the intake of fermented milk with Lactobacillus casei DN114001 in lactating mothers and their children

British Journal Of Nutrition ◽

10.1017/s0007114508959183 ◽

2008 ◽

Vol 100 (4) ◽

pp. 834-845 ◽

Cited By ~ 33

Author(s):

Adriana Ortiz-Andrellucchi ◽

Almudena Sánchez-Villegas ◽

Carlos Rodríguez-Gallego ◽

Angelina Lemes ◽

Teresa Molero ◽

...

Keyword(s):

Immune System ◽

Breast Feeding ◽

Lactobacillus Casei ◽

Lactation Period ◽

T Helper ◽

Mature Milk ◽

Double Blind ◽

Maternal Milk ◽

Breast Fed ◽

Helper Type

The healthy action of probiotics is not only due to their nutritional properties and their influence on the gastrointestinal environment, but also to their action on the immune system. The aim of the present study was to determine if 6 weeks of probiotic intake would be able to modulate the immune system in women who had recently delivered and were breast-feeding. The design consisted of a randomised, controlled and double-blind nutritional intervention study with parallel groups with a sample size of 104 women. The main variable is the T helper type 1/T helper type 2 (Th1/Th2) profile determined by measuring interferon-γ (Th1) and IL-4 (Th2) values in peripheral blood by flow cytometry. The modifications of cytokines were evaluated in maternal milk by cytometric bead array in a flow cytometer and ELISA at three stages of breast-feeding: colostrum, early milk (10 d) and mature milk (45 d). Additionally, the anthropometry and infectious and allergic episodes in the newborn were followed up throughout the first 6 months of life. After the consumption of milk fermented with Lactobacillus casei during the puerperium, we observed a non-significant increase in T and B lymphocytes and a significant increase in natural killer cells. A decrease in the pro-inflammatory cytokine TNF-α in maternal milk and fewer gastrointestinal disturbances were also observed in the breast-fed child of the mothers who consumed L. casei. The intake of milk fermented with L. casei during the lactation period modestly contributes to the modulation of the mother's immunological response after delivery and decreases the incidence of gastrointestinal episodes in the breast-fed child.

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