Chronic Illness Research Center, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Box 646534, Pullman, WA 99164-6534, USA.
Cancer Immunol Immunother. 2010 Aug;59(8):1151-9. doi: 10.1007/s00262-010-0837-x. Epub 2010 Mar 13.
We previously found that chronic alcohol consumption decreases the survival of mice bearing subcutaneous B16BL6 melanoma. The underlying mechanism is still not completely understood. Antitumor T cell immune responses are important to inhibiting tumor progression and extending survival. Therefore, we examined the effects of chronic alcohol consumption on the functionality and regulation of these cells in C57BL/6 mice that chronically consumed 20% (w/v) alcohol and subsequently were inoculated subcutaneously with B16BL6 melanoma cells. Chronic alcohol consumption inhibited melanoma-induced memory T cell expansion and accelerated the decay of interferon (IFN)-gamma producing T cells in the tumor-bearing mice. Foxp3(+)CD4(+)CD25(+) regulatory T cells were not affected; however, the percentage of myeloid-derived suppressor cells (MDSC) was significantly increased in the peripheral blood and spleen. T cell proliferation as determined by carboxyfluorescein succinimidyl ester labeling experiments in vitro was inhibited by alcohol consumption relative to control water-drinking melanoma-bearing mice. Collectively, these data show that chronic alcohol consumption inhibits proliferation of memory T cells, accelerates the decay of IFN-gamma producing CD8(+) T cells, and increases MDSC, all of which could be associated with melanoma progression and reduced survival.
我们之前发现,慢性酒精摄入会降低患有皮下 B16BL6 黑色素瘤的小鼠的存活率。其潜在机制仍不完全清楚。抗肿瘤 T 细胞免疫应答对于抑制肿瘤进展和延长生存时间非常重要。因此,我们研究了慢性酒精摄入对 C57BL/6 小鼠中这些细胞的功能和调节的影响,这些小鼠长期摄入 20%(w/v)酒精,随后皮下接种 B16BL6 黑色素瘤细胞。慢性酒精摄入抑制了黑色素瘤诱导的记忆 T 细胞扩增,并加速了荷瘤小鼠中产生干扰素(IFN)-γ的 T 细胞的衰减。Foxp3(+)CD4(+)CD25(+)调节性 T 细胞不受影响;然而,髓源抑制细胞(MDSC)的百分比在外周血和脾脏中显著增加。体外通过羧基荧光素琥珀酰亚胺酯标记实验测定的 T 细胞增殖被酒精消耗相对于对照饮水荷瘤小鼠受到抑制。综上所述,这些数据表明,慢性酒精摄入抑制记忆 T 细胞的增殖,加速产生 IFN-γ的 CD8(+)T 细胞的衰减,并增加 MDSC,所有这些都可能与黑色素瘤进展和生存时间缩短有关。