Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, USA.
Computer Science Department, Indiana University, Bloomington, IN, 47408, USA.
J Nanobiotechnology. 2023 Feb 4;21(1):40. doi: 10.1186/s12951-023-01786-6.
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.
癌症免疫疗法在治疗乳腺癌方面显示出巨大的潜力。尽管患者对辅助治疗的反应可能存在异质性，但预测个体患者对癌症免疫疗法的反应具有挑战性。在这里，我们报告了原代肿瘤衍生的器官型细胞簇（POCC），用于快速可靠地评估癌症免疫疗法。通过使用无标记、非接触和高度生物相容性的声流方法，可在 2 分钟内从患者原发性乳腺癌解离中组装数百个细胞簇。通过加入延时活细胞成像，POCC 可以忠实地再现癌症-免疫相互作用动力学及其对检查点抑制剂的反应。优于目前通常需要两周以上才能开发的肿瘤类器官，POCC 可在 12 小时内建立并用于评估癌症免疫疗法。由于培养时间短，POCC 可以保留来自原发性肿瘤的细胞成分。此外，POCC 可以以均匀的制造尺寸和细胞组成进行组装，并作为一个开放平台，在短周转时间内，在受控的治疗条件下操纵细胞组成和比例。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癌肿瘤并测试免疫疗法，以促进癌症的个体化治疗。
