Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy.

Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy.
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原发性肿瘤衍生的器官细胞簇的大声组装,用于快速评估癌症免疫疗法。

DOI:
10.1186/s12951-023-01786-6
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发表时间:
2023-02-04
影响因子:
10.2
通讯作者:
Guo, Feng
Guo, Feng
中科院分区:
工程技术1区
文献类型:
--
作者:
Wu, Zhuhao;Ao, Zheng;Cai, Hongwei;Li, Xiang;Chen, Bin;Tu, Honglei;Wang, Yijie;Lu, Rongze Olivia;Gu, Mingxia;Cheng, Liang;Lu, Xin;Guo, Feng

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癌症免疫疗法在治疗乳腺癌方面显示出很大的潜力。虽然患者可能对辅助治疗有不同的治疗反应,但预测单个患者对癌症免疫治疗的反应是具有挑战性的。在这里,我们报告了用于快速和可靠地评估癌症免疫治疗的原代肿瘤衍生器官型细胞团(POCCs)。通过使用一种无标记、非接触和高度生物兼容的声流控方法,可以在2分钟内从患者的原发乳腺肿瘤解离中组装数百个细胞团。通过加入延时活细胞成像,POCC可以真实地概括癌症-免疫相互作用的动力学以及它们对检查点抑制剂的反应。与目前需要两周以上培养的肿瘤器官相比,POCCs可以在12小时内建立并用于肿瘤免疫治疗的评估。由于培养时间短,POCCs可以保存原发肿瘤的细胞成分。此外,POCCs可以以均匀的制备尺寸和单元组成进行组装,并作为开放平台在受控处理条件下以较短的周转时间操纵单元组成和比例。因此,我们提供了一种新的方法来识别潜在的免疫原性乳腺肿瘤和测试免疫治疗,促进个性化的癌症治疗。网上版载有补充材料,可在10.1186/s12951-023-01786-6查阅。
Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patient’s response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy. The online version contains supplementary material available at 10.1186/s12951-023-01786-6.
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