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Circadian Variation of Immune Mechanisms in Lung Cancer and the Role of Melatonin

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Melatonin and Melatonergic Drugs in Clinical Practice

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Abstract

New cancer immunotherapeutic strategies rely on recent advances in the knowledge of the mechanisms responsible for antitumor immunity. Immune parameters in humans show temporal variations related to circadian changes of total lymphocytes and specific lymphocyte subsets in the peripheral blood, with an inverse relationship of the total number of lymphocytes to plasma cortisol concentration and a direct correlation to plasma melatonin levels. Immune responses are characterized by nyctohemeral variations and are physiologically controlled by neuroendocrine pathways. The discoveries of the antitumor cytokine network underlay innovative anticancer immunotherapeutic approach, taking into account neuroendocrine and neuroimmune status of cancer patients. Lung cancer patients present anomalies of proportions and circadian variations of lymphocyte subsets, as well as of hormones and cytokines that may impair the interplay among different lymphocyte subpopulations and neuroendocrine system components, decisive for an efficient immune response. A chronobiologic strategy of correctly timed circadian stage-dependent sampling and/or dosing schedule taking in consideration circadian rhythmicity in biochemical, physiological, and behavioral processes will be critical in any attempts to successfully optimize and personalize decision-making when evaluating immunomodulatory effects determined by biological response modifiers and adoptive immunotherapy protocols, in addition to neuroendocrine endogenous molecules, such as the pineal indole melatonin.

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Abbreviations

CCL20:

Chemokine (C–C motif) ligand 20

CCR6:

Chemokine (C–C motif) receptor 6

CTLA-4:

Cytotoxic T-lymphocyte antigen 4

EGF:

Epidermal growth factor

Foxp3:

Forkhead transcription factors

GH:

Growth hormone

GITR:

Glucocorticoid-induced TNF-α receptor

GVHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem cell transplantation

IFN:

Interferon

IGF:

Insulin-like growth factor

IL:

Interleukin

LAK:

Lymphokine-activated killer cells

MHC:

Major histocompatibility complex

MLT-R:

Melatonin receptors

NAT:

N-acetyl-transferase

NK:

Natural killer

PD-1:

Programmed death-1

PKC:

Protein kinase C

TCR:

T-cell receptors

TNF:

Tumor necrosis factor

TRH:

Thyrotropin-releasing hormone

TSH:

Thyroid-stimulating hormone

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Authors and Affiliations

  1. Division of Internal Medicine and Chronobiology Unit, Department of Medical Sciences, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo Della Sofferenza” Opera Di Padre Pio Da Pietrelcina, Cappuccini Avenue, S. Giovanni Rotondo, 71013, FG, Italy

    Gianluigi Mazzoccoli MD

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  1. Gianluigi Mazzoccoli MD
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Correspondence to Gianluigi Mazzoccoli MD .

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Editors and Affiliations

  1. Sri Sathya Sai Medical Educational and Research Foundation, An International Medical Sciences Research Center, Coimbatore, Tamil Nadu, India

    V. Srinivasan

  2. Department of Obstetrics and Gynecology, Hadassah Hebrew-University Medical Center, Jerusalem, Israel

    Amnon Brzezinski

  3. Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey

    Sukru Oter

  4. Department of Psychiatry Behavioral Sciences, Mercer University School of Medicine, Macon, Georgia, USA

    Samuel D. Shillcutt

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Mazzoccoli, G. (2014). Circadian Variation of Immune Mechanisms in Lung Cancer and the Role of Melatonin. In: Srinivasan, V., Brzezinski, A., Oter, S., Shillcutt, S. (eds) Melatonin and Melatonergic Drugs in Clinical Practice. Springer, New Delhi. https://doi.org/10.1007/978-81-322-0825-9_10

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  • DOI: https://doi.org/10.1007/978-81-322-0825-9_10

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  • Online ISBN: 978-81-322-0825-9

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