Doraneh-Gard Fatemeh, Amberger Daniel Christoph, Amend Carina, Weinmann Melanie, Schwepcke Christoph, Klauer Lara, Schutti Olga, Hosseini Hedayatollah, Krämer Doris, Rank Andreas, Schmid Christoph, Schmetzer Helga Maria
Medical Department III, Working-group Immune-Modulation, Klinikum Großhadern, Ludwig-Maximilians-University, 81377 Munich, Germany.
Bavarian Cancer Research Center (BZKF), 86156 Augsburg, Germany.
Cancers (Basel). 2024 Jun 28;16(13):2383. doi: 10.3390/cancers16132383.
Hypoxia can modulate the immune system by affecting the function and activity of immune cells, potentially leading to altered immune responses. This study investigated the generation of leukemia-derived dendritic cells (DC from leukemic blasts and their impact on immune cell activation under hypoxic (5-10% O) compared to normoxic (21% O) conditions using various immunomodulatory Kits. The results revealed that DC/DC-generation was similar under hypoxic and normoxic conditions, with no significant differences observed in frequencies of generated DC/DC. Furthermore, the study showed that the activation of immune cells and their anti-leukemic activity improved when T cell-enriched immunoreactive cells were co-cultured with DC/DC which were generated with Kit I and M compared to the control after mixed lymphocyte cultures. The anti-leukemic activity was improved under hypoxic compared to normoxic conditions after MLC. These findings suggest that DC/DC-cultures of leukemic whole blood with Kits under hypoxic conditions yield comparable frequencies of DC/DC and can even increase the anti-leukemic activity compared to normoxic conditions. Overall, this research highlights the potential of utilizing DC/DC (potentially induced in vivo with Kits) as a promising approach to enhance immune response in patients with acute myeloid leukemia.
缺氧可通过影响免疫细胞的功能和活性来调节免疫系统,这可能会导致免疫反应发生改变。本研究使用各种免疫调节试剂盒,调查了白血病来源的树突状细胞(由白血病原始细胞生成的DC)在低氧(5%-10% O₂)与常氧(21% O₂)条件下的生成情况及其对免疫细胞激活的影响。结果显示,低氧和常氧条件下DC/DC的生成情况相似,生成的DC/DC频率无显著差异。此外,研究表明,在混合淋巴细胞培养后,与对照组相比,当富含T细胞的免疫反应性细胞与用试剂盒I和M生成的DC/DC共培养时,免疫细胞的激活及其抗白血病活性得到改善。混合淋巴细胞培养后,与常氧条件相比,低氧条件下抗白血病活性有所提高。这些发现表明,在低氧条件下用试剂盒对白血病全血进行DC/DC培养可产生相当频率的DC/DC,与常氧条件相比甚至可增强抗白血病活性。总体而言,本研究突出了利用DC/DC(可能用试剂盒在体内诱导生成)作为增强急性髓系白血病患者免疫反应的一种有前景方法的潜力。