Chronic alcohol consumption enhances myeloid-derived suppressor cells in B16BL6 melanoma-bearing mice.
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.
Chronic Illness Research Center, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Box 646534, Pullman, WA 99164-6534, USA.
Hui
H
Zhang
Gary G
GG
Meadows
D000437:Alcoholism / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D007156:Immunologic Memory / Q000187:drug effects; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008546:Melanoma, Experimental / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000431:Ethanol; D007371:Interferon-gamma