Motamedi Masoumeh, Arab Samaneh, Moazzeni Seied Mohammad, Khamis Abadi Masoomeh, Hadjati Jamshid
Lorestan University of Medical Sciences, Khoramabad, Iran.
Clin Vaccine Immunol. 2009 Oct;16(10):1393-8. doi: 10.1128/CVI.00199-09. Epub 2009 Aug 5.
The use of dendritic cells (DCs) as a cellular adjuvant is a promising approach to the immunotherapy of cancer. It has previously been demonstrated that DCs pulsed ex vivo with Toxoplasma gondii antigens trigger a systemic Th1-biased specific immune response and induce protective and specific antitoxoplasma immunity. In the present study, we demonstrate that tumor antigen-pulsed DCs matured in the presence of Toxoplasma gondii components induce a potent antitumor response in a mouse model of fibrosarcoma. Bone-marrow derived DCs (BMDCs) were cultured in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. After 5 days, tumor lysates with or without the T. gondii lysate were added to the culture for another 2 days. The cytokine production in the BMDC culture and the coculture supernatants of DCs and splenic cells was evaluated. For immunization, 7 days after tumor challenge, different groups of BALB/c mice received different kinds of DCs subcutaneously around the tumor site. Tumor growth was monitored, and 2 weeks after DC immunotherapy, the cytotoxic activity and the infiltration of CD8(+) T cells were monitored in different groups. According to the findings, immunotherapy with T. gondii-matured DCs led to a significant increase in the activity of cytotoxic T cells and decreased the rate of growth of the tumor in immunized animals. Immature DCs did not cause any change in cytotoxic activity or the tumor growth rate compared to that in the healthy controls. The current study suggests that a specific antitumor immune response can be induced by DCs matured with T. gondii components and provide the basis for the use of T. gondii in DC-targeted clinical therapies.
使用树突状细胞（DCs）作为细胞佐剂是癌症免疫治疗的一种有前景的方法。先前已经证明，用弓形虫抗原在体外脉冲处理的DCs可引发全身性的以Th1为主的特异性免疫反应，并诱导保护性和特异性抗弓形虫免疫。在本研究中，我们证明在弓形虫成分存在下成熟的肿瘤抗原脉冲DCs在纤维肉瘤小鼠模型中诱导出有效的抗肿瘤反应。在粒细胞-巨噬细胞集落刺激因子和白细胞介素-4存在下培养骨髓来源的DCs（BMDCs）。5天后，将含有或不含有弓形虫裂解物的肿瘤裂解物加入培养物中再培养2天。评估BMDC培养物以及DCs与脾细胞共培养上清液中的细胞因子产生情况。为了进行免疫，在肿瘤攻击7天后，不同组的BALB/c小鼠在肿瘤部位周围皮下接受不同种类的DCs。监测肿瘤生长情况，并且在DC免疫治疗2周后，监测不同组中的细胞毒性活性和CD8(+) T细胞浸润情况。根据研究结果，用弓形虫成熟的DCs进行免疫治疗导致免疫动物中细胞毒性T细胞活性显著增加，并降低了肿瘤生长速率。与健康对照相比，未成熟的DCs在细胞毒性活性或肿瘤生长速率方面未引起任何变化。当前研究表明，用弓形虫成分成熟的DCs可诱导特异性抗肿瘤免疫反应，并为在以DC为靶点的临床治疗中使用弓形虫提供了依据。
