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首页> 外文期刊>Translational research: the journal of laboratory and clinical medicine >Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish
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Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish

机译：斑马鱼中人类癌细胞异种移植的新型免疫耐受

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Immune deficiency or suppression in host animals is an essential precondition for the success of cancer cell xenotransplantation because the host immune system has a tendency to reject implanted cells. However, in such animals, the typical tumor microenvironment seen in cancer subjects does not form because of the lack of normal immunity. Here, we developed a novel zebrafish (Danio rerio) model based on 2 rounds of cancer cell xenotransplantation that achieved cancer-specific immunologic tolerance without immunosuppression. We irradiated human cancer cells (PC-3, K562 and HepG2) to abolish their proliferative abilities and implanted them into zebrafish larvae. These cells survived for 2 weeks in the developing host. Three months after the first implantation, the zebrafish were implanted with the same, but nonirradiated, cell lines. These cancer cells proliferated and exhibited metastasis without immune suppression. To reveal the transcriptional mechanism of this immune tolerance, we conducted dual RNA-seq of the tumor with its surrounding tissues and identified several regulatory zebrafish genes that are involved in immunity; the expression of plasminogen activator, urokinase, and forkhead box P3 was altered in response to immunologic tolerance. In conclusion, this xenograft method has potential as a platform for zebrafish-based anticancer drug discovery because it can closely mimic human clinical cancers without inducing immune suppression.
机译：宿主动物的免疫缺陷或抑制是癌细胞异种移植成功的重要前提，因为宿主免疫系统具有排斥移植细胞的趋势。然而，在这类动物中，由于缺乏正常的免疫力，所以未形成在癌症受试者中看到的典型的肿瘤微环境。在这里，我们基于两轮癌细胞异种移植开发了一种新型的斑马鱼（Danio rerio）模型，该模型实现了癌症特异性的免疫耐受而没有免疫抑制作用。我们辐照了人类癌细胞（PC-3，K562和HepG2）以消除它们的增殖能力，并将其植入斑马鱼幼虫中。这些细胞在发育中的宿主中存活2周。第一次植入后三个月，斑马鱼植入了相同但未照射的细胞系。这些癌细胞增殖并显示出转移而没有免疫抑制。为了揭示这种免疫耐受的转录机制，我们对肿瘤及其周围组织进行了双重RNA-seq鉴定，并鉴定了与免疫有关的几种调节性斑马鱼基因。纤溶酶原激活物，尿激酶和叉头盒P3的表达因免疫耐受而改变。总之，这种异种移植方法有可能作为基于斑马鱼的抗癌药物发现的平台，因为它可以紧密模拟人类临床癌症而不会引起免疫抑制。

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