UPMC Hillman Cancer Center, Pittsburgh, PA, United States; Tsinghua University School of Medicine, Beijing, China.
UPMC Hillman Cancer Center, Pittsburgh, PA, United States; Carnegie Mellon University, Pittsburgh, PA, United States.
Cell Immunol. 2019 Jan;335:59-67. doi: 10.1016/j.cellimm.2018.10.011. Epub 2018 Nov 1.
Alpha fetoprotein (AFP) is produced by over 50% of hepatocellular carcinomas (HCC). Uptake of tumor-derived AFP (tAFP) can impair activity of human dendritic cells (DC). The expression pattern of the lipid antigen presenting genes from the CD1 family is reduced in AFP-treated monocyte-derived DC. Surface CD1 family proteins, particularly CD1d, were reduced in AFP-exposed DC (by both normal cord blood-derived AFP (nAFP) and tAFP). NKT cells recognize lipid antigens presented by CD1d molecules. They play an important role in connecting the innate and adaptive immune systems, and in anti-tumor immunity. We hypothesized that AFP might impair the ability of DC to stimulate natural killer T (NKT) cells. No significant impact of AFP was observed on NKT cell stimulation. By examining secreted cytokines, we observed non-significant AFP-induced changes in several secreted proteins. These data indicate that AFP downregulates CD1 molecules on DC, but the impact on NKT cell activations is minimal.
甲胎蛋白（AFP）是由超过 50%的肝细胞癌（HCC）产生的。肿瘤衍生的 AFP（tAFP）的摄取会损害人类树突状细胞（DC）的活性。在 AFP 处理的单核细胞衍生的 DC 中，脂质呈递基因的表达模式减少。表面 CD1 家族蛋白，特别是 CD1d，在 AFP 暴露的 DC 中减少（正常脐带血来源的 AFP（nAFP）和 tAFP 均可减少）。NKT 细胞识别由 CD1d 分子呈递的脂质抗原。它们在连接先天和适应性免疫系统以及抗肿瘤免疫中发挥重要作用。我们假设 AFP 可能会损害 DC 刺激自然杀伤 T（NKT）细胞的能力。未观察到 AFP 对 NKT 细胞刺激有显著影响。通过检查分泌的细胞因子，我们观察到 AFP 诱导的几种分泌蛋白的变化无显著意义。这些数据表明 AFP 下调了 DC 上的 CD1 分子，但对 NKT 细胞激活的影响很小。
