Rapid Profiling of Tumor-Immune Interaction Using Acoustically Assembled Patient-Derived Cell Clusters.
Rapid Profiling of Tumor-Immune Interaction Using Acoustically Assembled Patient-Derived Cell Clusters.
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使用声学组装的患者衍生细胞簇快速分析肿瘤-免疫相互作用。
DOI：
10.1002/advs.202201478
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发表时间：
2022-08
期刊：
影响因子：
15.1
通讯作者：
Guo, Feng
中科院分区：
文献类型：
--
作者：
Ao, Zheng;Wu, Zhuhao;Cai, Hongwei;Hu, Liya;Li, Xiang;Kaurich, Connor;Chang, Jackson;Gu, Mingxia;Liang, Cheng;Lu, Xin;Guo, Feng
关键词：
肿瘤微环境串扰，特别是癌细胞、T细胞和骨髓源性抑制细胞（MDSCs）之间的相互作用，介导肿瘤的发生、进展和对治疗的反应。然而，目前的患者衍生模型，如肿瘤类器官和2D培养缺乏一些必要的生态位细胞类型（例如，MDSCs），并且无法模拟复杂的肿瘤免疫相互作用。在这里，作者提出了一种新的声学组装患者来源的细胞团簇（apcc），它可以保存原始的肿瘤/免疫细胞组成，在3D微环境中模拟它们的相互作用，并以快速、可扩展和用户友好的方式测试原发性肿瘤的治疗反应。通过在细胞外基质中加入大量3D声学陷阱，在培养皿中可以在2分钟内组装数百个apcc。此外，apcc可以保存肿瘤诱导的MDSCs的敏感性和短寿命（≈1至2天的体内寿命），并模拟它们对T细胞肿瘤毒性的动态抑制长达24小时。最后，使用apcc，作者成功地模拟了靶向MDSCs的多激酶抑制剂（cabozantinib）和抗PD - 1免疫检查点抑制剂（pembrolizumab）的联合治疗效果。新型apcc在预测个性化癌症辅助治疗的治疗反应以及筛查新型癌症免疫治疗和联合治疗方面具有很大的潜力。声学组装患者来源的细胞团用于复杂的肿瘤微环境串扰的快速分析报道。该方法已被证明可以成功地模拟癌细胞、T细胞和短寿命髓系抑制细胞在24小时内的相互作用。该方法在预测个性化癌症辅助治疗的治疗反应和筛选新的癌症治疗方法方面具有很大的潜力。
Tumor microenvironment crosstalk, in particular interactions between cancer cells, T cells, and myeloid‐derived suppressor cells (MDSCs), mediates tumor initiation, progression, and response to treatment. However, current patient‐derived models such as tumor organoids and 2D cultures lack some essential niche cell types (e.g., MDSCs) and fail to model complex tumor‐immune interactions. Here, the authors present the novel acoustically assembled patient‐derived cell clusters (APCCs) that can preserve original tumor/immune cell compositions, model their interactions in 3D microenvironments, and test the treatment responses of primary tumors in a rapid, scalable, and user‐friendly manner. By incorporating a large array of 3D acoustic trappings within the extracellular matrix, hundreds of APCCs can be assembled within a petri dish within 2 min. Moreover, the APCCs can preserve sensitive and short‐lived (≈1 to 2‐day lifespan in vivo) tumor‐induced MDSCs and model their dynamic suppression of T cell tumor toxicity for up to 24 h. Finally, using the APCCs, the authors succesully model the combinational therapeutic effect of a multi‐kinase inhibitor targeting MDSCs (cabozantinib) and an anti‐PD‐1 immune checkpoint inhibitor (pembrolizumab). The novel APCCs may hold promising potential in predicting treatment response for personalized cancer adjuvant therapy as well as screening novel cancer immunotherapy and combinational therapy. Acoustically assembled patient‐derived cell clusters for the rapid profiling of complicated tumor microenvironment crosstalk are reported. This method is demonstrated to successfully model interactions among cancer cells, T cells, and short‐lived myeloid‐derived suppressor cells within 24 h. This method holds promising potential in predicting treatment response for personalized cancer adjuvant therapy and screening novel cancer treatments.
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影响因子：
30.5
作者：
Goldmann T;Wieghofer P;Jordão MJ;Prutek F;Hagemeyer N;Frenzel K;Amann L;Staszewski O;Kierdorf K;Krueger M;Locatelli G;Hochgerner H;Zeiser R;Epelman S;Geissmann F;Priller J;Rossi FM;Bechmann I;Kerschensteiner M;Linnarsson S;Jung S;Prinz M
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影响因子：
158.5
作者：
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通讯作者：
Powles, T.
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