Abstract 4716: Chronic alcohol consumption activates the LiTAF pathway in melanoma-bearing mice.

We previously reported that chronic alcohol consumption increases myeloid-derived suppressor cells (MDSC) and compromises melanoma-specific CD8+ T cells in B16BL6 melanoma-bearing mice; however, the underlying mechanism has not been elucidated. Activation of LPS-induced TNF-α factor (LiTAF) gene leads to up-regulation in the expression of various cytokines, chemokines and growth factors such as TNF-α, IL-1β, and VEGF, which are inducers of MDSC. Alcohol consumption is associated with the leakage of LPS into the blood. However, it is not known whether alcohol consumption modulates the expression of LiTAF. Herein, we examined the effects of alcohol and subcutaneous inoculation of melanoma in mice on the expression of LiTAF and its downstream cytokines, chemokines and growth factors. Female C57BL/6 mice were given 20% (w/v) alcohol for three to six months followed by subcutaneous inoculation of 2x105 B16BL6 melanoma cells. Two weeks after tumor inoculation, the expression of LiTAF and related cytokine genes in the spleen were examined by RT-PCR. Chronic alcohol consumption dramatically up regulated the expression of LiTAF in the spleen of melanoma-bearing mice; however, expression was almost undetectable in the spleen of corresponding water-drinking mice. The expression of IL-1β, IL-10, TNF-α, CCL5, and VEGF-β was also significantly up regulated by alcohol. These results indicate that chronic alcohol consumption activates the LiTAF pathway and up regulates the expression of the downstream cytokines, chemokines and growth factors. The up regulation of these cytokines could contribute to the induction of MDSC and inhibition on CD8+ T cells. (Supported by funds received from the Summer Undergraduate Research Fellowship (SURF) Program, from NIH grants R01 AA07193 and K05AA017149, and from funds provided for medical and biological research by the State of Washington Initiative Measure No. 171). Citation Format: Andrew Marron, Hui Zhang, Zhaohui Zhu, Gary G. Meadows. Chronic alcohol consumption activates the LiTAF pathway in melanoma-bearing mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4716. doi:10.1158/1538-7445.AM2013-4716