Steinborn Carmen, Klemd Amy Marisa, Sanchez-Campillo Ann-Sophie, Rieger Sophie, Scheffen Marieke, Sauer Barbara, Garcia-Käufer Manuel, Urech Konrad, Follo Marie, Ücker Annekathrin, Kienle Gunver Sophia, Huber Roman, Gründemann Carsten
Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Verein für Krebsforschung, Arlesheim, Switzerland.
PLoS One. 2017 Jul 18;12(7):e0181553. doi: 10.1371/journal.pone.0181553. eCollection 2017.
Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays. Furthermore, we examined whether VAEI was able to counteract tumor-induced immunosuppression within this cellular system using a renal cancer cell model. The role of mistletoe lectin (ML) was analyzed using ML-specific antibodies and ML-depleted VAEI. VAEI and VAEA augmented the maturation of dendritic cells. VAEI abrogated tumor-induced immunosuppression of dendritic cells and both processes were partially mediated by ML since ML-depleted VAEI and ML-specific antibodies almost neutralized the rehabilitative effects of VAEI on DC maturation. Using these settings, co-culture experiments with purified CD4+ T cells had no influence on T cell proliferation and activation but did have an impact on IFN-γ secretion. The study provides a potential mode-of-action of VAE as an additive cancer therapy based on immunomodulatory effects. However, the impact on the in vivo situation has to be evaluated in further studies.
肿瘤细胞能够分泌免疫抑制物质，以降低树突状细胞（DC）的活性，从而逃避免疫反应。槲寄生（欧洲槲寄生）提取物（VAE）常作为辅助抗癌疗法用于刺激免疫反应，但其影响尚不清楚。利用人类细胞系统，通过流式细胞术、自动荧光显微镜和细胞因子珠阵列分析，研究了两种不同的VAE（VAEA + VAEI）对人类树突状细胞成熟和T细胞功能的影响。此外，我们使用肾癌细胞模型研究了VAEI是否能够在该细胞系统中抵消肿瘤诱导的免疫抑制。使用ML特异性抗体和去除ML的VAEI分析了槲寄生凝集素（ML）的作用。VAEI和VAEA增强了树突状细胞的成熟。VAEI消除了肿瘤诱导的树突状细胞免疫抑制，这两个过程部分由ML介导，因为去除ML的VAEI和ML特异性抗体几乎中和了VAEI对DC成熟的恢复作用。在这些条件下，与纯化的CD4 + T细胞进行共培养实验对T细胞增殖和激活没有影响，但对IFN-γ分泌有影响。该研究提供了VAE作为基于免疫调节作用的辅助癌症治疗的潜在作用模式。然而，对体内情况的影响必须在进一步研究中进行评估。
