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Alcohol Consumption and Antitumor Immunity: Dynamic Changes from Activation to Accelerated Deterioration of the Immune System

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Book cover Biological Basis of Alcohol-Induced Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 815))

Abstract

The molecular mechanisms of how alcohol and its metabolites induce cancer have been studied extensively. However, the mechanisms whereby chronic alcohol consumption affects antitumor immunity and host survival have largely been unexplored. We studied the effects of chronic alcohol consumption on the immune system and antitumor immunity in mice inoculated with B16BL6 melanoma and found that alcohol consumption activates the immune system leading to an increase in the proportion of IFN-γ-producing NK, NKT, and T cells in mice not injected with tumors. One outcome associated with enhanced IFN-γ activation is inhibition of melanoma lung metastasis. However, the anti-metastatic effects do not translate into increased survival of mice bearing subcutaneous tumors. Continued growth of the subcutaneous tumors and alcohol consumption accelerates the deterioration of the immune system, which is reflected in the following: (1) inhibition in the expansion of memory CD8+ T cells, (2) accelerated decay of Th1 cytokine-producing cells, (3) increased myeloid-derived suppressor cells, (4) compromised circulation of B cells and T cells, and (5) increased NKT cells that exhibit an IL-4 dominant cytokine profile, which is inhibitory to antitumor immunity. Taken together, the dynamic effects of alcohol consumption on antitumor immunity are in two opposing phases: the first phase associated with immune stimulation is tumor inhibitory and the second phase resulting from the interaction between the effects of alcohol and the tumor leads to immune inhibition and resultant tumor progression.

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Acknowledgement

This project was supported by K05AA017149 and by funds provided for medical and biological research by the State of Washington Initiative Measure No. 171.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, 99210-1495, USA

    Hui Zhang, Zhaohui Zhu, Faya Zhang & Gary G. Meadows

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  1. Hui Zhang
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  2. Zhaohui Zhu
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  3. Faya Zhang
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  4. Gary G. Meadows
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Corresponding author

Correspondence to Hui Zhang .

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Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the United States, Washington, District of Columbia, USA

    Samir Zakhari

  3. Centre of Alcohol Research, University of Heidelberg, Germany and Salem Medical Centre, Heidelberg, Germany

    Helmut K. Seitz

  4. Department of Pathology, Anatomy, & Cell, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Jan B. Hoek

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Zhang, H., Zhu, Z., Zhang, F., Meadows, G.G. (2015). Alcohol Consumption and Antitumor Immunity: Dynamic Changes from Activation to Accelerated Deterioration of the Immune System. In: Vasiliou, V., Zakhari, S., Seitz, H., Hoek, J. (eds) Biological Basis of Alcohol-Induced Cancer. Advances in Experimental Medicine and Biology, vol 815. Springer, Cham. https://doi.org/10.1007/978-3-319-09614-8_18

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