title: Alcohol consumption and antitumor immunity: dynamic changes from activation to accelerated deterioration of the immune system.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, 99210-1495, USA, hzhang@wsu.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.forename: Faya
authors.initials: F
authors.lastname: Zhang
authors.forename: Gary G
authors.initials: GG
authors.lastname: Meadows
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000431:Ethanol / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000431:Ethanol; D007371:Interferon-gamma