Chronic alcohol consumption inhibits melanoma growth but decreases the survival of mice immunized with tumor cell lysate and boosted with α-galactosylceramide.
Chronic alcohol consumption inhibits melanoma growth but decreases the survival of mice immunized with tumor cell lysate and boosted with α-galactosylceramide.
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长期饮酒会抑制黑色素瘤的生长，但会降低用肿瘤细胞裂解物免疫并用α-半乳糖神经酰胺增强的小鼠的存活率。
DOI：
10.1016/j.intimp.2015.06.018
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发表时间：
2015
影响因子：
5.6
通讯作者：
Zhang,Hui
中科院分区：
文献类型：
--
作者：
Zhang,Faya;Zhu,Zhaohui;Meadows,GaryG;Zhang,Hui
饮酒会增加多种癌症的发病率。然而，长期饮酒如何影响肿瘤进展和宿主存活率仍然在很大程度上未被探索。使用小鼠B16 BL 6黑色素瘤模型，我们研究了长期饮酒对皮下注射的影响。肿瘤生长、iNKT细胞抗肿瘤免疫应答和宿主存活。结果表明，虽然长期饮酒抑制黑色素瘤生长，但这并不能转化为宿主存活率的增加。用黑色素瘤细胞裂解物免疫小鼠不会显著增加饮水的荷黑色素瘤小鼠的中位生存期，但显著增加饮酒的荷黑色素瘤小鼠的中位生存期。尽管免疫后饮酒小鼠的生存期延长，但中位生存期与饮水组的免疫小鼠没有差异。与相应的未免疫小鼠相比，用肿瘤细胞裂解物免疫并结合α-半乳糖神经酰胺激活iNKT细胞显著增加了两组荷黑素瘤小鼠的宿主存活率;然而，饮酒组的中位存活率显著低于饮水组。饮酒增加了胸腺和血液中的NKT细胞，并使荷瘤小鼠的NKT细胞因子谱从Th 1为主向Th 2为主倾斜。总之，这些结果表明，长期饮酒会激活免疫系统，从而抑制s.c.黑色素瘤生长并增强对黑色素瘤裂解物免疫的免疫应答。随着肿瘤的进展，饮酒会加速iNKT细胞功能障碍并损害抗肿瘤免疫力，从而导致荷黑色素瘤小鼠的存活率降低。
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.