title: Comparison of circadian characteristics for cytotoxic lymphocyte subsets in non-small cell lung cancer patients versus controls.
abstract: Lymphocyte subsets are major cellular components of the adaptive immune response and in most cases show 24-h (circadian) variations in health. In order to determine overall levels and circadian characteristics of cytotoxic natural killer (NK) and T and B lymphocyte subsets, blood samples were collected every 4 h for 24 h from eleven male controls (C) without neoplastic disease and nine men with untreated non-small cell lung cancer (NSCLC) and analyzed for 3 hormones (melatonin, cortisol, and interleukin 2 [IL2]) and for 11 lymphocyte subpopulations classified by cell surface clusters of differentiation (CD) and antigen receptors. Circadian rhythmicity for each variable was evaluated by ANOVA and 24 h cosine fitting and groups compared. Rhythms in melatonin and cortisol (peaks near 01:30 and 08:00 h) indicated identical synchronization to the light-dark schedule and probable persistent entrainment of rhythms for both groups in metabolism or proliferation of healthy tissues normally tightly coupled to the sleep-wake cycle. Twenty-four hours means were significantly higher in NSCLC for CD16, CD25, cortisol, and IL2 and lower for CD8, CD8bright, and γδTCR. A significant circadian rhythm was found in C with daytime peaks for CD8, CD8dim, CD16, Vδ2TCR, and cortisol and nighttime peaks for CD3, CD4, CD20, and melatonin, and in NSCLC, with daytime peaks for CD16, γδTCR, Vδ2TCR and cortisol, and nighttime peaks for CD4, CD25, and melatonin. Thus, NSCLC was associated with significant increases or decreases in proportions for several lymphocyte subsets that may reflect disease development, but peak times were nevertheless similar between C and NSCLC for each variable, suggesting that timed circadian administration (chronotherapy) of immunotherapy and other cancer treatments may improve efficacy due to persistent circadian entrainment of healthy tissues.
authors: Department of Internal Medicine and Chronobiology Unit, Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy. g.mazzoccoli@tin.it
authors: Gianluigi
authors: G
authors: Mazzoccoli
authors: Robert B
authors: RB
authors: Sothern
authors: Paola
authors: P
authors: Parrella
authors: Lucia A
authors: LA
authors: Muscarella
authors: Vito Michele
authors: VM
authors: Fazio
authors: Francesco
authors: F
authors: Giuliani
authors: Victoria
authors: V
authors: Polyakova
authors: Igor M
authors: IM
authors: Kvetnoy
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015992:Body Mass Index; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D002940:Circadian Rhythm; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D007694:Killer Cells, Natural; D016014:Linear Models; D018655:Lymphocyte Count; D008297:Male; D008550:Melatonin / Q000097:blood; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D008550:Melatonin; D006854:Hydrocortisone