Abstract 314: The interaction between chronic alcohol consumption and melanoma skews the iNKT cell cytokine profile towards IL-4 dominance

Abstract

Abstract Despite the growing evidence that alcohol consumption is associated with the incidence of many different types of cancer, there is little research regarding the effect of continued alcohol consumption on growth, progression and subsequent survival of cancer patients. Using a well-established mouse model we previously found that chronic alcohol consumption impairs the anti-melanoma functions of CD8+T cells and NK cells, and this leads to decreased survival of melanoma-bearing mice. The underlying mechanism for these effects is not known. Herein we examined the relationship of NKT cells to regulation of anti-tumor responses in alcohol consuming mice since NKT cells play important roles in the regulation of the anti-tumor immune response. The phenotype and function of invariant (i)NKT cells were examined in female B16BL6-bearing C57BL6 mice given 20% alcohol for three months. We found that alcohol consumption increased iNKT cells in the liver of mice not inoculated with melanoma, but did not alter iNKT cells in other organs. iNKT cells were dramatically increased in the blood and liver of chronic alcohol consuming, melanoma-bearing mice; however, these cells were not increased in the spleen or draining lymph nodes. Immature NK1.1- iNKT cells decreased 2-4 fold in the blood, spleen and liver of the alcohol-consuming, melanoma-bearing mice, suggesting that alcohol interacting with the melanoma tumors stimulates iNKT cells maturation. Upon activation, fewer iNKT cells produced IFN-gamma in these mice compared to water-drinking, melanoma-bearing mice. The ratio of IL-4:IFN-gamma-producing iNKT cells increased 2-fold as a result of the alcohol/tumor interaction, thus skewing the cytokine profile toward Th2 dominance. The Th2 dominant cytokine profile could negatively regulate the anti-tumor activities of CD8+ T cell and NK cells as well as increase myeloid derived suppressor cells, which we previously reported. Collectively, these data support an important role for iNKT cells in regulation of melanoma progression. (Supported by NIH grants R01AA07293 and K05AA017149, and WSU Alcohol and Drug Abuse Research Program grant 13B-2957-1246). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 314. doi:1538-7445.AM2012-314