title: Chronic alcohol consumption inhibits melanoma growth but decreases the survival of mice immunized with tumor cell lysate and boosted with α-galactosylceramide.
abstract: Alcohol consumption increases the incidence of multiple types of cancer. However, how chronic alcohol consumption affects tumor progression and host survival remains largely unexplored. Using a mouse B16BL6 melanoma model, we studied the effects of chronic alcohol consumption on s.c. tumor growth, iNKT cell antitumor immune response, and host survival. The results indicate that although chronic alcohol consumption inhibits melanoma growth, this does not translate into increased host survival. Immunizing mice with a melanoma cell lysate does not significantly increase the median survival of water-drinking, melanoma-bearing mice, but significantly increases the median survival of alcohol-consuming, melanoma-bearing mice. Even though survival is extended in the alcohol-consuming mice after immunization, the median survival is not different from the immunized mice in the water-drinking group. Immunization with tumor cell lysate combined with α-galatosylceramide activation of iNKT cells significantly increases host survival of both groups of melanoma-bearing mice compared to their respective non-immunized counterparts; however, the median survival of the alcohol-consuming group is significantly lower than that of the water-drinking group. Alcohol consumption increases NKT cells in the thymus and blood and skews NKT cell cytokine profile from Th1 dominant to Th2 dominant in the tumor-bearing mice. In summary, these results indicate that chronic alcohol consumption activates the immune system, which leads to the inhibition of s.c. melanoma growth and enhances the immune response to immunization with melanoma lysate. With tumor progression, alcohol consumption accelerates iNKT cell dysfunction and compromises antitumor immunity, which leads to decreased survival of melanoma-bearing mice.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, United States.
authors.forename: Faya
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, United States.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, United States.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Meadows
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, United States. Electronic address: hzhang@wsu.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000428:Alcohol Drinking / Q000276:immunology*; D000818:Animals; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D047368:Tumor Burden
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Alcohol; Melanoma; NKT cells; Survival