Cells, cytokines, chemokines, and cancer stress: A biobehavioral study of patients with chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied. Before the first dose, a validated self-report measure of stress (the Impact of Event Scale) was completed, and blood was drawn for absolute lymphocyte counts (ALCs) and for cytokine and chemokine enzyme-linked immunosorbent assays. Multiple linear regression models tested stress as a concurrent predictor of ALCs; of cytokines (tumor necrosis factor α [TNFα], a proliferation-inducing ligand [APRIL], B-cell activating factor [BAFF], interleukin 6 [IL-6], IL-10, IL-16, and vascular endothelial growth factor [VEGF]); and of the chemokine (C-C motif) ligand 3 (CCL3). RESULTS: Controlling for relevant demographic variables, comorbidities, CLL genetic risk (deletion of the short arm of chromosome 17 [del17p]), and correlates of inflammation, stress predicted higher ALCs (P < .05), and higher levels of TNFα (P < .05), IL-16 (P < .01), and CCL3 (P < .05). Stress was not associated with APRIL, BAFF, IL-6, IL-10, or VEGF. CONCLUSIONS: Novel biobehavioral data from patients with relapsed/refractory CLL demonstrate that stress is related to heightened levels of cellular, cytokine, and chemokine markers associated previously with progressive disease in CLL. The current results indicate that stress is related to immune and inflammatory processes that contribute to cancer cell proliferation and survival. These data provide a first look into these processes. Cancer 2018. © 2018 American Cancer Society.

Trajectories of Stress, Depressive Symptoms, and Immunity in Cancer Survivors: Diagnosis to 5 Years.

PURPOSE: Five-year disease endpoint trajectories are available for every cancer site. In contrast, there are few longitudinal, biobehavioral studies of survivors extending beyond the first or second year following diagnosis. This gap is addressed with stress, depressive symptom, and immunity data from breast cancer patients followed continuously for 5 years. EXPERIMENTAL DESIGN: Women (N = 113) diagnosed and surgically treated for breast cancer and awaiting adjuvant therapy completed self-report measures of stress and depressive symptoms and provided blood for immune assays [natural killer cell cytotoxicity (NKCC) and T-cell blastogenesis]. Assessments (N = 12) were repeated every 4 to 6 months for 5 years. RESULTS: Multiphase linear mixed models show phases of change and identified specific time points of change. Cancer stress shows two distinct phases of decline, with the change point being 12 months. In contrast, a steep decline in depressive symptoms occurs by 7 months, with stable, low levels thereafter. NKCC shows a steady upward trajectory through 18 months and upper limit stability thereafter, whereas there was no reliable trajectory for T-cell blastogenesis. CONCLUSIONS: For the first time, trajectories and specific time points of change in biobehavioral data for breast cancer survivors are provided, traced through 5 years. Following diagnosis, the breast survivor experience is one of a co-occurrence of change (recovery) in psychologic and innate immunity markers from diagnosis to18 months, and a pattern of stability (depression, NKCC) or continued improvement (stress) through year 5. These data provide new directions for survivorship care and detail of the biobehavioral trajectory. Clin Cancer Res; 23(1); 52-61. ©2016 AACR.