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 mean 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.

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice

“…We next determined how alcohol consumption affects body weight change during the acute phase of MCMV infection. In this chronic alcohol consumption model, alcohol consumption does not affect body weight . Body weight was measured before MCMV infection (day 0).…”

“…In this chronic alcohol consumption model, alcohol consumption does not affect body weight. 40 Body weight was measured before MCMV infection (day 0). There was no difference in the average body weight between the two groups of mice ( Figure 1C).…”

Alcohol intake aggravates adipose browning and muscle atrophy in cancer-associated cachexia

“…RA blocks white adipogenesis via inhibiting Zfp423 expression [ 41 ]; on the other hand, RA upregulates the expression of brown adipogenic genes, activates BAT and induces the formation of thermogenic beige adipocytes [ 28 , 42 – 44 ]. While the thermogenic activity of brown and beige adipocytes increases energy expenditure which contributes to obesity prevention, it causes unfavorable consequences in cancer patients [ 2 , 3 , 12 ]; the elevated energy expenditure and body weight loss increase mortality [ 45 ]. Currently, RA is commonly used in cancer prevention and treatment [ 46 – 48 ], and our data suggest the negative impact of RA treatment in dissipating energy needed for patients, especially those with late stage cancers.…”

“…The treatment group was provided with chow and 20% (w/v) alcohol diluted from 190-proof Everclear (St. Louis, MO) with sterilized Milli-Q water. Similar doses of alcohol have been used in our previous studies [ 28 , 45 , 55 ]. After 3 months, mice in each group were further divided into two sub-groups with/without tumor inoculation.…”

Alcohol exposure differentially effects anti-tumor immunity in females by altering dendritic cell function

“…The impact of alcohol on cancer risk remains inconclusive due to seemingly conflicting data in several reports (Allen et al, 2009; Brandon-Warner, Walling, Schrum, & McKillop, 2012; Fowke, Howard, Andriole, & Freedland, 2014; Garcia-Lavandeira, Ruano-Ravina, & Barros-Dios, 2016; Gong et al, 2009; Meadows & Zhang, 2015; Newcomb et al, 2013; F. Zhang, Zhu, Meadows, & Zhang, 2015).…”