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Comparison of circadian characteristics for cytotoxic lymphocyte subsets in non-small cell lung cancer patients versus controls

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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.

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Acknowledgments

We wish to express our gratitude and thank the control subjects and NSCLC patients that each volunteered to participate in this study.

Conflict of interest

The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine and Chronobiology Unit, Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia, Italy

    Gianluigi Mazzoccoli

  2. The Rhythmometry Laboratory, College of Biological Sciences, University of Minnesota, St. Paul, MN, USA

    Robert B. Sothern

  3. Research Laboratory of Oncology, Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia, Italy

    Paola Parrella, Lucia A. Muscarella & Vito Michele Fazio

  4. Computing Unit, Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia, Italy

    Francesco Giuliani

  5. Department of Cell Biology and Pathology, Institute of Bioregulation and Gerontology and Russian Academy for Medical Sciences, St. Petersburg, Russia

    Victoria Polyakova & Igor M. Kvetnoy

  6. Department of Pathology, Ott Institute of Obstetrics and Gynecology, Russian Academy for Medical Sciences, St. Petersburg, Russia

    Victoria Polyakova & Igor M. Kvetnoy

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  1. Gianluigi Mazzoccoli
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Correspondence to Gianluigi Mazzoccoli.

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Mazzoccoli, G., Sothern, R.B., Parrella, P. et al. Comparison of circadian characteristics for cytotoxic lymphocyte subsets in non-small cell lung cancer patients versus controls. Clin Exp Med 12, 181–194 (2012). https://doi.org/10.1007/s10238-011-0153-6

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  • DOI: https://doi.org/10.1007/s10238-011-0153-6

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