中文摘要：
癌症免疫编辑是肿瘤细胞与免疫系统之间动态相互作用的过程。在本研究中，我们探索了快速斑马鱼异种移植模型，以研究先天免疫在这一过程中的作用。通过使用多种乳腺癌和结直肠癌细胞系及zAvatars，我们发现一些细胞在斑马鱼异种移植中被清除（消退者），而另一些则成功植入（进展者）。我们重点研究来自同一患者的两种人类结直肠癌细胞，它们表现出截然不同的植入/清除特征。使用多克隆异种移植以模拟肿瘤内异质性，我们证明SW620_进展者可以阻止SW480_消退者的清除。SW480_消退者比SW620_进展者更有效地招募巨噬细胞和中性粒细胞；然而，SW620_进展者会使巨噬细胞向促肿瘤表型转化。通过基因和化学方法抑制髓系细胞表明，巨噬细胞和中性粒细胞在清除过程中起关键作用。单细胞转录组分析显示快速的亚克隆选择，其中消退亚克隆的清除与IFN/Notch信号相关，而逃逸扩展亚克隆则富集IL10通路。总体而言，我们的工作为使用斑马鱼异种移植模型作为肿瘤微环境的活体生物标志物提供了可能性。
英文摘要：
Cancer immunoediting is a dynamic process of crosstalk between tumor cells and the immune system. Herein, we explore the fast zebrafish xenograft model to investigate the innate immune contribution to this process. Using multiple breast and colorectal cancer cell lines and zAvatars, we find that some are cleared (regressors) while others engraft (progressors) in zebrafish xenografts. We focus on two human colorectal cancer cells derived from the same patient that show contrasting engraftment/clearance profiles. Using polyclonal xenografts to mimic intra-tumor heterogeneity, we demonstrate that SW620_progressors can block clearance of SW480_regressors. SW480_regressors recruit macrophages and neutrophils more efficiently than SW620_progressors; SW620_progressors however, modulate macrophages towards a pro-tumoral phenotype. Genetic and chemical suppression of myeloid cells indicates that macrophages and neutrophils play a crucial role in clearance. Single-cell-transcriptome analysis shows a fast subclonal selection, with clearance of regressor subclones associated with IFN/Notch signaling and escaper-expanded subclones with enrichment of IL10 pathway. Overall, our work opens the possibility of using zebrafish xenografts as living biomarkers of the tumor microenvironment.
论文信息：
论文题目：Innate immune evasion revealed in a colorectal zebrafish xenograft model
期刊名称：Nature Communications
时间期卷：12, Article number: 1156 (2021)
在线时间：2021年2月19日
DOI：doi.org/10.1038/s41467-021-21421-y
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes& Control liposomes
办事处：Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体斑马鱼巨噬细胞，疾病模型为：斑马鱼异种移植模型。斑马鱼模型已成为研究肿瘤生物学及其与免疫系统相互作用的强有力工具。斑马鱼具有高度保守的脊椎动物先天免疫系统，包括补体、Toll样受体、中性粒细胞和具有吞噬活性的巨噬细胞。另一个优势是适应性免疫系统的成熟要在受精后 2–3 周才出现。这为体内独立于适应性系统研究先天免疫反应提供了时间窗口。此外，透明性允许实时细胞间相互作用成像，并且基因操作的可行性使得构建报告基因系和突变体成为可能。荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：在结直肠斑马鱼异种移植模型中揭示的先天免疫逃避。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法文字描述：
For the selective depletion of macrophages, Liposomes-encapsulated PBS (L-PBS) and Liposomes-encapsulated clodronate (L-Clodronate) were purchased from Liposoma. At the time of cell resuspension immediately prior to cell microinjection into zebrafish, cells were resuspended either in PBS, L-PBS, or L-Clodronate at a final concentration of 0.25 × 106 cells/μL.
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法文献截图：
