Leplina Olga Yu, Tyrinova Tamara V, Tikhonova Marina A, Ostanin Alexander A, Chernykh Elena R
Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia(1).
Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia(1).
Cytokine. 2015 Jan;71(1):1-7. doi: 10.1016/j.cyto.2014.07.258. Epub 2014 Sep 16.
Dendritic cell-based vaccines are considered as a new and promising immunotherapeutic approach for cancer treatment. However, the choice of optimal protocol of dendritic cell generation in vitro represents the major challenge. Here, we compared phenotype and functional characteristics of human monocyte-derived dendritic cells (DCs) generated in the presence of IL-4/GM-CSF (IL4-DCs) and IFNα/GM-CSF (IFN-DCs). We showed that IFN-DCs displayed semi-mature phenotype and expressed higher level of CD123, TNF-related apoptosis-inducing ligand (TRAIL) and B7-H1 molecules in comparison with IL4-DCs. LPS-stimulated IFN-DCs were characterized by greater production of Th1/pro-inflammatory (IFN-γ, IL-2, IL-1β, TNF-α, IL-17), Тh2/anti-inflammatory cytokines (IL-10, IL-5), hematopoietic growth factors (G-CSF) and chemokines (MCP-1). These data indicated more pronounced ability of IFN-DCs to induce cellular immune response as well as humoral immune response compared to IL4-DCs. LPS-stimulated IFN-DCs possessed higher direct cytotoxic activity against TRAIL-sensitive tumor cell line Jurkat and similar cytotoxicity against TRAIL-resistant tumor HEp-2 cells. Besides, IFN-DCs and IL4-DCs equally induced apoptosis of activated CD4(+) and CD8(+) T cells. These results suggest that IFN-DCs can be used as potent cell-based curative therapies for individuals with cancer.
基于树突状细胞的疫苗被认为是一种用于癌症治疗的新型且有前景的免疫治疗方法。然而，体外生成树突状细胞的最佳方案的选择是主要挑战。在此，我们比较了在IL-4/GM-CSF（IL4-DCs）和IFNα/GM-CSF（IFN-DCs）存在下生成的人单核细胞衍生树突状细胞（DCs）的表型和功能特征。我们发现，与IL4-DCs相比，IFN-DCs呈现半成熟表型，且CD123、肿瘤坏死因子相关凋亡诱导配体（TRAIL）和B7-H1分子表达水平更高。LPS刺激的IFN-DCs的特征在于Th1/促炎细胞因子（IFN-γ、IL-2、IL-1β、TNF-α、IL-17）、Th2/抗炎细胞因子（IL-10、IL-5）、造血生长因子（G-CSF）和趋化因子（MCP-1）的产生更多。这些数据表明，与IL4-DCs相比，IFN-DCs诱导细胞免疫应答以及体液免疫应答的能力更显著。LPS刺激的IFN-DCs对TRAIL敏感的肿瘤细胞系Jurkat具有更高的直接细胞毒性活性，对TRAIL抗性肿瘤HEp-2细胞具有相似的细胞毒性。此外，IFN-DCs和IL4-DCs同等程度地诱导活化的CD4(+)和CD8(+) T细胞凋亡。这些结果表明，IFN-DCs可作为针对癌症患者的有效的基于细胞的治疗方法。
