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

Abstract 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...

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Main Authors: Zhuhao Wu, Zheng Ao, Hongwei Cai, Xiang Li, Bin Chen, Honglei Tu, Yijie Wang, Rongze Olivia Lu, Mingxia Gu, Liang Cheng, Xin Lu, Feng Guo
Format: Article
Language:English
Published: BMC 2023-02-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-023-01786-6
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author Zhuhao Wu
Zheng Ao
Hongwei Cai
Xiang Li
Bin Chen
Honglei Tu
Yijie Wang
Rongze Olivia Lu
Mingxia Gu
Liang Cheng
Xin Lu
Feng Guo
author_facet Zhuhao Wu
Zheng Ao
Hongwei Cai
Xiang Li
Bin Chen
Honglei Tu
Yijie Wang
Rongze Olivia Lu
Mingxia Gu
Liang Cheng
Xin Lu
Feng Guo
author_sort Zhuhao Wu
collection DOAJ
description Abstract 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.
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spelling doaj.art-681412411ac64529a06a805cee72a4a82023-02-05T12:22:44ZengBMCJournal of Nanobiotechnology1477-31552023-02-012111910.1186/s12951-023-01786-6Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapyZhuhao Wu0Zheng Ao1Hongwei Cai2Xiang Li3Bin Chen4Honglei Tu5Yijie Wang6Rongze Olivia Lu7Mingxia Gu8Liang Cheng9Xin Lu10Feng Guo11Department of Intelligent Systems Engineering, Indiana UniversityDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Intelligent Systems Engineering, Indiana UniversityComputer Science Department, Indiana UniversityDepartment of Neurological Surgery, Brain Tumor Center, Helen Diller Family Comprehensive Cancer Center, University of California San FranciscoCenter for Stem Cell and Organoid Medicine (CuSTOM), Division of Pulmonary Biology, Division of Developmental Biology, Cincinnati Children’s Hospital Medical CenterDepartment of Pathology and Laboratory Medicine, Brown University Warren Alpert Medical School, Lifespan Academic Medical Center, and the Legorreta Cancer Center at Brown UniversityDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre DameDepartment of Intelligent Systems Engineering, Indiana UniversityAbstract 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.https://doi.org/10.1186/s12951-023-01786-6MicrofluidicsAcoustofluidicsCell clustersCancer modelsCancer immunotherapy
spellingShingle Zhuhao Wu
Zheng Ao
Hongwei Cai
Xiang Li
Bin Chen
Honglei Tu
Yijie Wang
Rongze Olivia Lu
Mingxia Gu
Liang Cheng
Xin Lu
Feng Guo
Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
Journal of Nanobiotechnology
Microfluidics
Acoustofluidics
Cell clusters
Cancer models
Cancer immunotherapy
title Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
title_full Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
title_fullStr Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
title_full_unstemmed Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
title_short Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
title_sort acoustofluidic assembly of primary tumor derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
topic Microfluidics
Acoustofluidics
Cell clusters
Cancer models
Cancer immunotherapy
url https://doi.org/10.1186/s12951-023-01786-6
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