Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Scand J Immunol. 2014 Jun;79(6):415-22. doi: 10.1111/sji.12172.
Antigen-loaded dendritic cells (DCs) used as anticancer vaccine holds promise for therapy, but needs to be optimized. The most frequently described DC vaccine is being matured with a cocktail containing prostaglandin E2 (PGE2 DC). However, even though PGE2 DCs express both costimulatory and migratory receptors, their IL-12p70-prodcution is low, leading to an insufficient Th1 immune response. As an alternative, α-type-1 polarized DCs (αDC1s) have shown a superior production of IL-12p70 and subsequent activation of effector cells. From chronic lymphocytic leukaemia (CLL) patients, αDC1s can be generated to induce a functional Th1-immune response. Yet, another costimulatory receptor, CD70, appears to be essential for optimal DC function by promotion of T cell survival and function. So far, PGE2 is suggested as one of the most important factors for the induction of CD70 expression on DCs. Therefore, we wanted to investigate whether αDC1s have the ability to express functional CD70. We found that CD70 expression on αDC1s could be upregulated in the same manner as PGE2 DCs. In an allogeneic mixed leucocyte reaction, we found that antibody-blocking of CD70 on αDC1s from controls reduced effector cell proliferation although this could not be found when using CLL αDC1s. Nevertheless, CD70-blocking of αDC1s from both controls and patients with CLL had a negative influence on the production of both IL-12p70 and the Th1 cytokine IFN-γ, while the production of the Th2 cytokine IL-5 was enhanced. Together, this study further suggests that αDC1s should be considered as a suitable candidate for clinical antitumour vaccine strategies in patients with CLL.
负载抗原的树突状细胞 (DC) 作为抗癌疫苗具有治疗潜力，但需要进行优化。最常描述的 DC 疫苗是用包含前列腺素 E2 (PGE2 DC) 的鸡尾酒来成熟。然而，尽管 PGE2 DC 表达共刺激和迁移受体，但它们的 IL-12p70 产生量低，导致 Th1 免疫反应不足。作为替代方案，α 型 1 极化的 DCs (αDC1s) 表现出更高的 IL-12p70 产生和随后的效应细胞激活。从慢性淋巴细胞白血病 (CLL) 患者中，可以生成 αDC1s 来诱导功能性 Th1 免疫反应。然而，另一个共刺激受体 CD70 似乎通过促进 T 细胞存活和功能对于最佳 DC 功能至关重要。到目前为止，PGE2 被认为是诱导 DC 上 CD70 表达的最重要因素之一。因此，我们想研究 αDC1s 是否有能力表达功能性 CD70。我们发现，αDC1s 上的 CD70 表达可以像 PGE2 DC 一样被上调。在同种异体混合白细胞反应中，我们发现阻断对照来源的 αDC1s 上的 CD70 减少了效应细胞增殖，尽管使用 CLL αDC1s 时没有发现这种情况。然而，阻断对照和 CLL 患者的 αDC1s 上的 CD70 对 IL-12p70 和 Th1 细胞因子 IFN-γ 的产生都有负面影响，而 Th2 细胞因子 IL-5 的产生则增强。总之，这项研究进一步表明，αDC1s 应该被认为是 CLL 患者临床抗肿瘤疫苗策略的合适候选者。
