Abstract 3660: Chronic alcohol consumption inhibits iNKT cell activation-induced antitumor response in B16BL6 melanoma-bearing mice

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Alcohol consumption increases the incidence of many types of cancer including melanoma. It is not well understand how chronic alcohol consumption affects tumor progression and survival. We previously found that chronic alcohol consumption activates CD8+ T cells in the non-tumor injected mice and at the early stage after tumor inoculation; however, it accelerates CD8+T cell dysfunction during further tumor growth. The underlying mechanism regarding modulation of CD8+ T cells by alcohol and how the functional changes in the immune response affect tumor growth and survival remain to be elucidated. Herein, we investigated how alcohol modulates iNKT cells in melanoma-bearing mice and how different immune treatment regimens affect tumor growth and survival. We found that alcohol increases iNKT cells in non-tumor injected mice, and that activation of these iNKT cells induces a Th1 response. With tumor progression, alcohol reverses iNKT cell cytokine profile to aTh2-dominant one. Chronic alcohol consumption inhibits melanoma growth, but this is does associated with increased survival. Immunization with a melanoma cell lysate significantly inhibits tumor growth and increases survival compared to the non-immunized alcohol-consuming, tumor-bearing mice. Immunization in the water-drinking control mice did not significantly increase survival compared to respective non-immunized mice. Immunization coupled with iNKT cell activation with alpha GalCer significantly increases the survival of water-drinking melanoma-bearing mice. However, the survival of mice consuming alcohol was significantly decreased compared to their water-drinking counterparts. Collectively, chronic alcohol consumption interacting with melanoma alters the iNKT cell cytokine profile from Th1-dominant to Th2- dominant, which in turn contributes to inhibition of antitumor immunity and decreases survival of melanoma-bearing mice. Supported by NIH grants R01AA07293 and K05AA017149 and funds provided for medical and biological research by the State of Washington Initiative Measure No. 171. Citation Format: Hui Zhang, Faya Zhang, ZhaoHui Zhu, Gary G. Meadows. Chronic alcohol consumption inhibits iNKT cell activation-induced antitumor response in B16BL6 melanoma-bearing mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3660. doi:10.1158/1538-7445.AM2014-3660