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首页> 外文期刊>Alcohol >Alcohol exposure differentially effects anti-tumor immunity in females by altering dendritic cell function
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Alcohol exposure differentially effects anti-tumor immunity in females by altering dendritic cell function

机译：通过改变树突细胞功能，酒精暴露差异地影响女性中的抗肿瘤免疫力

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Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of an anti-tumor response, especially in the context of generation of an immune vaccine has not been examined. In the clinic, DC vaccines are typically generated from autologous blood, therefore prior exposure to substances such as alcohol may be a critical factor to consider regarding the effectiveness in generating an immune response. In this study, we demonstrate for the first time that ethanol differentially affects DC and tumor Ag-specific T cell responses depending on sex. Signaling pathways were found to be differentially regulated in DC in females compared to males and these differences were exacerbated by ethanol treatment. DC from female mice treated with ethanol were unable to activate Ag-specific cytotoxic T cells (CTL) as shown by reduced expression of CD44, CD69, and decreased production of granzyme B and IFN gamma. Furthermore, although FOXO3, an immune suppressive mediator of DC function, was found to be upregulated in DC from female mice, ethanol related suppression was independent of FOXO3. These findings demonstrate for the first time differential impacts of alcohol on the immune system of females compared to males and may be a critical consideration for determining the effectiveness of an immune based therapy for cancer in patients that consume alcohol. (C) 2016 The Authors. Published by Elsevier Inc.
机译：树突状细胞（DCS）是抗肿瘤免疫的关键组分，因为它们诱导抗原（Ag）诱导鲁棒免疫应答的能力。以前证明了醇以降低DC能力呈现异物，并促进在感染和创伤的情况下的促炎反应。然而，尚未检查酒精暴露对抗肿瘤反应产生的影响，特别是在产生免疫疫苗的上下文中。在诊所，DC疫苗通常由自体血液产生，因此在诸如醇的物质之前可能是考虑产生免疫应答的有效性的关键因素。在这项研究中，我们首次证明了乙醇差异地影响DC和肿瘤特异性T细胞反应根据性别。发现信号传导途径与雄性相比，雌性的DC中的差异调节，并通过乙醇处理加剧了这些差异。通过乙醇处理的雌性小鼠的DC不能激活Ag特异性细胞毒性T细胞（CT1），如通过降低CD44，CD69和Crenzyme B和IFNγ的产生降低的表达所示。此外，虽然FOXO3，DC功能的免疫抑制介质介质，但在雌性小鼠的DC中被上调，但乙醇相关抑制与FOXO3无关。这些研究结果证明了与男性相比，醇对雌性的免疫系统对免疫系统的差异影响，并且可能是测定患者患者患者癌症的免疫基础治疗的有效性的关键考虑因素。 （c）2016年作者。 elsevier公司发布

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