中文摘要：

癌癥免疫編輯是腫瘤細(xì)胞與免疫系統(tǒng)之間動(dòng)態(tài)相互作用的過程。在本研究中，我們探索了快速斑馬魚異種移植模型，以研究先天免疫在這一過程中的作用。通過使用多種乳腺癌和結(jié)直腸癌細(xì)胞系及zAvatars，我們發(fā)現(xiàn)一些細(xì)胞在斑馬魚異種移植中被清除（消退者），而另一些則成功植入（進(jìn)展者）。我們重點(diǎn)研究來自同一患者的兩種人類結(jié)直腸癌細(xì)胞，它們表現(xiàn)出截然不同的植入/清除特征。使用多克隆異種移植以模擬腫瘤內(nèi)異質(zhì)性，我們證明SW620_進(jìn)展者可以阻止SW480_消退者的清除。SW480_消退者比SW620_進(jìn)展者更有效地招募巨噬細(xì)胞和中性粒細(xì)胞；然而，SW620_進(jìn)展者會(huì)使巨噬細(xì)胞向促腫瘤表型轉(zhuǎn)化。通過基因和化學(xué)方法抑制髓系細(xì)胞表明，巨噬細(xì)胞和中性粒細(xì)胞在清除過程中起關(guān)鍵作用。單細(xì)胞轉(zhuǎn)錄組分析顯示快速的亞克隆選擇，其中消退亞克隆的清除與IFN/Notch信號(hào)相關(guān)，而逃逸擴(kuò)展亞克隆則富集IL10通路?？傮w而言，我們的工作為使用斑馬魚異種移植模型作為腫瘤微環(huán)境的活體生物標(biāo)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.

論文信息：

論文題目：Innate immune evasion revealed in a colorectal zebrafish xenograft model

期刊名稱：Nature Communications

時(shí)間期卷：12, Article number: 1156 (2021)

在線時(shí)間：2021年2月19日

DOI：doi.org/10.1038/s41467-021-21421-y

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes& Control liposomes

辦事處：Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體斑馬魚巨噬細(xì)胞，疾病模型為：斑馬魚異種移植模型。斑馬魚模型已成為研究腫瘤生物學(xué)及其與免疫系統(tǒng)相互作用的強(qiáng)有力工具。斑馬魚具有高度保守的脊椎動(dòng)物先天免疫系統(tǒng)，包括補(bǔ)體、Toll樣受體、中性粒細(xì)胞和具有吞噬活性的巨噬細(xì)胞。另一個(gè)優(yōu)勢是適應(yīng)性免疫系統(tǒng)的成熟要在受精后 2–3 周才出現(xiàn)。這為體內(nèi)獨(dú)立于適應(yīng)性系統(tǒng)研究先天免疫反應(yīng)提供了時(shí)間窗口。此外，透明性允許實(shí)時(shí)細(xì)胞間相互作用成像，并且基因操作的可行性使得構(gòu)建報(bào)告基因系和突變體成為可能。荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：在結(jié)直腸斑馬魚異種移植模型中揭示的先天免疫逃避。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法文字描述：

Zebrafish macrophage ablation with clodronate liposomes

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巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法文獻(xiàn)截圖：