Cited by 1463D Printing in Biomedical ResearchCellular Mechanics and InteractionsHydrogels: synthesis, properties, applications

The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.

An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment

Open access

Aung, Aereas, Kumar, Vardhman, Theprungsirikul, Jomkuan, Davey, Shruti K., Varghese, Shyni·2020·Cancer Research

DOI 10.1158/0008-5472.can-19-0342PMC PMC8545579

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Recruitment of immune cells to a tumor is determined by the complex interplay between cellular and noncellular components of the tumor microenvironment. Ex vivo platforms that enable identification of key components that promote immune cell recruitment to the tumor could advance the field significantly. Herein, we describe the development of a perfusable multicellular tumor-on-a-chip platform involving different cell populations. Cancer cells, monocytes, and endothelial cells were spatially confined within a gelatin hydrogel in a controlled manner by using 3D photopatterning. The migration of the encapsulated endothelial cells against a chemokine gradient created an endothelial layer around the constructs. Using this platform, we examined the effect of cancer cell–monocyte interaction on T-cell recruitment, where T cells were dispersed within the perfused media and allowed to infiltrate. The hypoxic environment in the spheroid cultures recruited more T cells compared with dispersed cancer cells. Moreover, the addition of monocytes to the cancer cells improved T-cell recruitment. The differences in T-cell recruitment were associated with differences in chemokine secretion including chemokines influencing the permeability of the endothelial barrier. This proof-of-concept study shows how integration of microfabrication, microfluidics, and 3D cell culture systems could be used for the development of tumor-on-a-chip platforms involving heterotypic cells and their application in studying recruitment of cells by the tumor-associated microenvironment. Significance: This study describes how tumor-on-chip platforms could be designed to create a heterogeneous mix of cells and noncellular components to study the effect of the tumor microenvironment on immune cell recruitment.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-19-0342

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407222 · Cited by 5,413
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
The immune contexture in cancer prognosis and treatment
Fridman, W. H., Zitvogel, L., Sautès–Fridman, C., & Kroemer, G. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.101 · Cited by 2,263
Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy
Nagarsheth, N., Wicha, M. S., & Zou, W. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.49 · Cited by 2,251
Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Gettinger, S. N., Horn, L., Gandhi, L., Spigel, D. R., Antonia, S. J., Rizvi, N. A., Powderly, J. D., Heist, R. S., Carvajal, R. D., Jackman, D. M., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.58.3708 · Cited by 1,196
Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment
Harlin, H., Meng, Y., Peterson, A. C., Zha, Y., Tretiakova, M., Slingluff, C., McKee, M., & Gajewski, T. F. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2281 · Cited by 1,121
M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide
Genin, M., Clement, F., Fattaccioli, A., Raes, M., & Michiels, C. (2015) · BMC Cancer · doi:10.1186/s12885-015-1546-9 · Cited by 1,090
Hypoxia-Inducible Factors: Master Regulators of Cancer Progression
Schito, L., & Semenza, G. L. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.10.016 · Cited by 962

Show all 50 references

Sorted by citations

Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research
Pinto, B., Henriques, A. C., Silva, P. M. A., & Bousbaa, H. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12121186 · Cited by 440
3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions
Rodrigues, J., Heinrich, M. A., Teixeira, L. M., & Prakash, J. (2021) · Trends in Cancer · doi:10.1016/j.trecan.2020.10.009 · Cited by 405
“The results showed greater T cell infiltration when monocytes were present in the culture, and also when higher levels of hypoxia were emulated by using tumor spheroids instead of dispersed cancer cells [71].”
BackgroundMethod
Tumor microenvironment: barrier or opportunity towards effective cancer therapy
Tiwari, A., Trivedi, R., & Lin, S. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00866-3 · Cited by 399
Microfluidics for Drug Development: From Synthesis to Evaluation
Liu, Y., Sun, L., Zhang, H., Shang, L., & Zhao, Y. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01289 · Cited by 211
Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy
Liu, Z., Zhou, Z., Dang, Q., Xu, H. M., Lv, J., Li, H., & Han, X. (2022) · Theranostics · doi:10.7150/thno.76854 · Cited by 200
3D Tumor Models and Their Use for the Testing of Immunotherapies
Boucherit, N., Gorvel, L., & Olive, D. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.603640 · Cited by 188
Emerging trends in organ-on-a-chip systems for drug screening
Wang, Y., Gao, Y., Pan, Y., Zhou, D., Liu, Y., Yin, Y. B., Yang, J., Wang, Y., & Song, Y. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.02.006 · Cited by 132
Advances in Organ-on-a-Chip Materials and Devices
Nahak, B. K., Mishra, A., Preetam, S., & Tiwari, A. (2022) · ACS Applied Bio Materials · doi:10.1021/acsabm.2c00041 · Cited by 128
Immunotherapy discovery on tumor organoid-on-a-chip platforms that recapitulate the tumor microenvironment
Zhang, J., Tavakoli, H., Ma, L., Li, X., Han, L., & Li, X. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114365 · Cited by 110
The role of tumor microenvironment in drug resistance: emerging technologies to unravel breast cancer heterogeneity
Salemme, V., Centonze, G., Avalle, L., Natalini, D., Piccolantonio, A., Arina, P., Morellato, A., Ala, U., Taverna, D., Turco, E., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1170264 · Cited by 106
Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research
Düzağaç, F., Saorin, G., Memeo, L., Canzonieri, V., & Rizzolio, F. (2021) · Cancers · doi:10.3390/cancers13040737 · Cited by 97
Electrospun nanofibers in cancer research: from engineering of in vitro 3D cancer models to therapy
Cavo, M., Serio, F., Kale, N. R., D'Amone, E., Gigli, G., & del Mercato, L. L. (2020) · Biomaterials Science · doi:10.1039/d0bm00390e · Cited by 95
Engineering approaches for studying immune-tumor cell interactions and immunotherapy
Shelton, S. E., Nguyen, H. T., Barbie, D. A., & Kamm, R. D. (2021) · iScience · doi:10.1016/j.isci.2020.101985 · Cited by 93
3D cancer models: One step closer to in vitro human studies
Manduca, N., Maccafeo, E., Maria, R. D., Sistigu, A., & Musella, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1175503 · Cited by 103
Microfluidic high-throughput 3D cell culture
Ko, J., Park, D., Lee, J., Jung, S., Baek, K., Sung, K. E., Lee, J., & Jeon, N. L. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00163-8 · Cited by 88
Organoids and organs-on-chips: insights into predicting the efficacy of systemic treatment in colorectal cancer
Zhu, J., Ji, L., Chen, Y., Li, H., Huang, M., Dai, Z., Wang, J., Xiang, D., Fu, G., Lei, Z., et al. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01354-9 · Cited by 92
Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis
Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 83
“Beyond fibroblasts, similar strategies have been used in immune-tumor spheroids to investigate how macrophages or T cells migrate in response to tumor-derived chemokines, influencing immune suppression, matrix remodeling, or drug resistance [289].”
Immunocompetent cancer-on-chip models to assess immuno-oncology therapy
Maulana, T. I., Kromidas, E., Wallstabe, L., Cipriano, M., Alb, M., Zaupa, C., Hudecek, M., Fogal, B., & Loskill, P. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.03.015 · Cited by 86
3D Culture Systems for Exploring Cancer Immunology
Fitzgerald, A. A., Li, E., & Weiner, L. M. (2020) · Cancers · doi:10.3390/cancers13010056 · Cited by 85
Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models
Blanco‐Fernandez, B., Gaspar, V. M., Engel, E., & Mano, J. F. (2021) · Advanced Science · doi:10.1002/advs.202003129 · Cited by 78
Harnessing 3D in vitro systems to model immune responses to solid tumours: a step towards improving and creating personalized immunotherapies
Zhou, Z., Pang, Y., Ji, J., He, J., Liu, T., Ouyang, L., Zhang, W., Zhang, X., Zhang, Z., Zhang, K., et al. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00896-4 · Cited by 79
Engineering microphysiological immune system responses on chips
Miller, C. P., Shin, W., Ahn, E. H., Kim, H. J., & Kim, D.-H. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2020.01.003 · Cited by 74
Cell and tissue engineering in lymph nodes for cancer immunotherapy
Najibi, A. J., & Mooney, D. J. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.023 · Cited by 73
Cancer-on-chip models for metastasis: importance of the tumor microenvironment
Jouybar, M., de Winde, C. M., Wolf, K., Friedl, P., Mebius, R. E., & den Toonder, J. M. J. (2024) · Trends in Biotechnology · doi:10.1016/j.tibtech.2023.10.001 · Cited by 66
Exploring Tumor–Immune Interactions in Co-Culture Models of T Cells and Tumor Organoids Derived from Patients
Jeong, S. Y., & Kang, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914609 · Cited by 74
Tumor-on-a-chip platforms to study cancer–immune system crosstalk in the era of immunotherapy
Parlato, S., Grisanti, G., Sinibaldi, G., Peruzzi, G., Casciola, C. M., & Gabriele, L. (2020) · Lab on a Chip · doi:10.1039/d0lc00799d · Cited by 69
A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model
Marzagalli, M., Pelizzoni, G., Fedi, A., Vitale, C., Fontana, F., Bruno, S., Poggi, A. D., Dondero, A., Aiello, M., Castriconi, R., et al. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.945149 · Cited by 63
3D Tumor Spheroid and Organoid to Model Tumor Microenvironment for Cancer Immunotherapy
Zhu, Y., Kang, E., Wilson, M., Basso, T., Chen, E., Yu, Y., & Li, Y.-R. (2022) · Organoids · doi:10.3390/organoids1020012 · Cited by 63
High-Throughput 3D In Vitro Tumor Vasculature Model for Real-Time Monitoring of Immune Cell Infiltration and Cytotoxicity
Song, J., Choi, H., Koh, S. K., Park, D., Yu, J., Kang, H., Kim, Y., Cho, D., & Jeon, N. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.733317 · Cited by 60
3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment
Franchi-Mendes, T., Eduardo, R., Domenici, G., & Brito, C. (2021) · Cancers · doi:10.3390/cancers13184610 · Cited by 59
In vitro immunity: an overview of immunocompetent organ-on-chip models
Morrison, A. I., Sjoerds, M. J., Vonk, L. A., Gibbs, S., & Koning, J. J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1373186 · Cited by 58
The Variety of 3D Breast Cancer Models for the Study of Tumor Physiology and Drug Screening
Fröhlich, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087116 · Cited by 51
Micro-engineering and nano-engineering approaches to investigate tumour ecosystems
Kim, M., Panagiotakopoulou, M., Chen, C., Ruiz, S. B., Ganesh, K., Tammela, T., & Heller, D. A. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00593-3 · Cited by 49
Advances in the application of 3D tumor models in precision oncology and drug screening
Guan, X., & Huang, S. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1021966 · Cited by 45
Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models
Moccia, C., & Haase, K. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.694218 · Cited by 49
Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS)
Malik, M., Yang, Y., Fathi, P., Mahler, G. J., & Esch, M. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.721338 · Cited by 43
Engineering in vitro immune-competent tissue models for testing and evaluation of therapeutics
Hammel, J. H., Zatorski, J. M., Cook, S. R., Pompano, R. R., & Munson, J. M. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114111 · Cited by 42
Microphysiological systems for solid tumor immunotherapy: opportunities and challenges
Abizanda-Campo, S., Virumbrales-Muñoz, M., Humayun, M., Mármol, I., Beebe, D. J., Ochoa, I., Oliván, S., & Ayuso, J. M. (2023) · Microsystems & Nanoengineering · doi:10.1038/s41378-023-00616-x · Cited by 42
A biomimetic liver cancer on-a-chip reveals a critical role of LIPOCALIN-2 in promoting hepatocellular carcinoma progression
Shen, P., Jia, Y., Zhou, W., Zheng, W., Wu, Y., Qu, S., Du, S., Wang, S., Shi, H., Sun, J., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.04.010 · Cited by 42
Engineered 3D ex vivo models to recapitulate the complex stromal and immune interactions within the tumor microenvironment
Ravi, K., Manoharan, T. J. M., Wang, K.-C., Pockaj, B. A., & Nikkhah, M. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122428 · Cited by 45
Understanding and improving cellular immunotherapies against cancer: From cell-manufacturing to tumor-immune models
Ringquist, R., Ghoshal, D., Jain, R., & Roy, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114003 · Cited by 39
Going with the Flow: Modeling the Tumor Microenvironment Using Microfluidic Technology
Xie, H., Appelt, J. W., & Jenkins, R. W. (2021) · Cancers · doi:10.3390/cancers13236052 · Cited by 41
Towards spatially-organized organs-on-chip: Photopatterning cell-laden thiol-ene and methacryloyl hydrogels in a microfluidic device
Ortiz-Cárdenas, J. E., Zatorski, J. M., Arneja, A., Montalbine, A. N., Munson, J. M., Luckey, C. J., & Pompano, R. R. (2022) · Organs-on-a-Chip · doi:10.1016/j.ooc.2022.100018 · Cited by 38
An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics
Kumar, V., Perikamana, S. K. M., Tata, A., Hoque, J., Gilpin, A., Tata, P. R., & Varghese, S. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.848699 · Cited by 36
Self-citation
Organ-on-chip platforms for nanoparticle toxicity and efficacy assessment: Advancing beyond traditional in vitro and in vivo models
Sampaio, A. R., Maia, R., Ciardulli, M. C., Santos, H. A., & Sarmento, B. F. C. C. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102053 · Cited by 39
Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs
Cipriano, M., Schlünder, K., Probst, C., Linke, K., Weiß, M., Fischer, M. J., Mesch, L., Achberger, K., Liebau, S., Mesquida, M., et al. (2022) · Communications Biology · doi:10.1038/s42003-021-02977-3 · Cited by 35
A 3D pancreatic tumor model to study T cell infiltration
Mollica, H., Teo, Y. J., Tan, A. S. M., Tan, D. Z. M., Decuzzi, P., Pavesi, A., & Adriani, G. (2021) · Biomaterials Science · doi:10.1039/d1bm00210d · Cited by 32
On-chip modeling of tumor evolution: Advances, challenges and opportunities
Li, C., Holman, J. B., Shi, Z., Qiu, B., & Ding, W. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100724 · Cited by 33
From cell spheroids to vascularized cancer organoids: Microfluidic tumor-on-a-chip models for preclinical drug evaluations
Wu, Y., Zhou, Y., Qin, X., & Liu, Y. (2021) · Biomicrofluidics · doi:10.1063/5.0062697 · Cited by 33
Opportunities and challenges to engineer 3D models of tumor-adaptive immune interactions
Visalakshan, R. M., Lowrey, M. K., Sousa, M. G. C., Helms, H. R., Samiea, A., Schutt, C. E., Moreau, J. M., & Bertassoni, L. E. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1162905 · Cited by 32
Nanobiotechnological approaches for breast cancer Management: Drug delivery systems and 3D In-Vitro models
Abolhassani, H., Eskandari, A., Poor, A. S., Zarrabi, A., Khodadadi, B., Karimifard, S., Sahrayi, H., Bourbour, M., & Yaraki, M. T. (2024) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2024.215754 · Cited by 35
Hot or cold: Bioengineering immune contextures into in vitro patient-derived tumor models
Too, N. S. H., Ho, N. C. W., Adine, C., Iyer, N. G., & Fong, E. L. S. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.05.001 · Cited by 32
Organ-on-a-chip platforms as novel advancements for studying heterogeneity, metastasis, and drug efficacy in breast cancer
Kalot, R., Mhanna, R., & Talhouk, R. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108156 · Cited by 31
Methods for Establishing a Renal Cell Carcinoma Tumor Spheroid Model With Immune Infiltration for Immunotherapeutic Studies
Lugand, L., Mestrallet, G., Laboureur, R., Dumont, C., Bouhidel, F. A., Djouadou, M., Masson-Lecomte, A., Desgrandchamps, F., Culine, S., Carosella, E. D., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.898732 · Cited by 29
The Peripheral Immune Landscape of Breast Cancer: Clinical Findings and In Vitro Models for Biomarker Discovery
Batalha, S., Cristóvão‐Ferreira, S., & Brito, C. (2021) · Cancers · doi:10.3390/cancers13061305 · Cited by 31
Tumor-on-a-chip: Perfusable vascular incorporation brings new approach to tumor metastasis research and drug development
Wang, R., Zhang, C., Li, D., & Yao, Y. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1057913 · Cited by 30
A review of organ-on-chip fabrication methods: From early developments to overcoming inert barriers
Olaizola‐Rodrigo, C., Bayona, C., Oliván, S., & Monge, R. (2025) · iScience · doi:10.1016/j.isci.2025.113992 · Cited by 31
Imaging microphysiological systems: a review
Peel, S. E., & Jackman, M. J. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00186.2020 · Cited by 31
Mediated Electrochemistry to Mimic Biology's Oxidative Assembly of Functional Matrices
Li, J., Kim, E., Gray, K. M., Conrad, C., Tsao, C., Wang, S. P., Zong, G., Scarcelli, G., Stroka, K. M., Wang, L., et al. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202001776 · Cited by 28
Engineered Tumor–Immune Microenvironment On A Chip to Study T Cell–Macrophage Interaction in Breast Cancer Progression
Manoharan, T. J. M., Ravi, K., Suresh, A. P., Acharya, A. P., & Nikkhah, M. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303658 · Cited by 27
PDAC as an immune evasive disease: can 3D model systems aid to tackle this clinical problem?
Narayanan, S., Vicent, S., & Ponz-Sarvisé, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.787249 · Cited by 24
3D-Printed Tumor-on-Chip for the Culture of Colorectal Cancer Microspheres: Mass Transport Characterization and Anti-Cancer Drug Assays
Sánchez-Salazar, M. G., Oliver, R. C.-L., Ramos-Meizoso, S., Jerezano-Flores, V. S., Gallegos-Martínez, S., Bolívar‐Monsalve, E. J., Ceballos‐González, C. F., Santiago, G. T., & Álvarez, M. M. (2023) · Bioengineering · doi:10.3390/bioengineering10050554 · Cited by 23
Mechanoimmunology in the solid tumor microenvironment
Golo, M., Newman, P. L. H., Kempe, D., & Biro, M. (2024) · Biochemical Society Transactions · doi:10.1042/bst20231427 · Cited by 23
Modeling the tumor immune microenvironment for drug discovery using 3D culture
Lee, J. Y., & Chaudhuri, O. (2021) · APL Bioengineering · doi:10.1063/5.0030693 · Cited by 22
Prediction of CAR‐T Therapy In Vitro: Development of Biomimetic Models for CAR‐T Killing Effect Assessment
Sun, X., Zhang, Z., Zhao, W., Xu, S., Zhang, J., ZhuanSun, X.-M., Ye, J., Han, Y., Gu, Z., & Chen, Z. (2025) · Small · doi:10.1002/smll.202503384 · Cited by 23
Evolution of Metastasis Study Models toward Metastasis‐On‐A‐Chip: The Ultimate Model?
Ruiz‐Espigares, J., Nieto, D., Moroni, L., Jiménez, G., & Marchal, J. A. (2021) · Small · doi:10.1002/smll.202006009 · Cited by 23
Diversity Models and Applications of 3D Breast Tumor-on-a-Chip
Song, K., Zu, X., Du, Z., Hu, Z., Wang, J., & Li, J. (2021) · Micromachines · doi:10.3390/mi12070814 · Cited by 21
3D Tumor Models for Breast Cancer: Whither We Are and What We Need
Balachander, G. M., Kotcherlakota, R., Nayak, B., Kedaria, D., Rangarajan, A., & Chatterjee, K. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00230 · Cited by 21
Myeloid-derived suppressor cells in cancer
Gao, J., Liu, W., Tang, Z., Fan, J., & Shi, Y. (2022) · iLiver · doi:10.1016/j.iliver.2022.06.002 · Cited by 21
Recent advances in cancer-on-a-chip tissue models to dissect the tumour microenvironment
Seaman, K., Sun, Y., & You, L. (2023) · Med-X · doi:10.1007/s44258-023-00011-1 · Cited by 24
Biofabrication approaches and regulatory framework of metastatic tumor‐on‐a‐chip models for precision oncology
Nieto, D., Jiménez, G., Moroni, L., López‐Ruiz, E., Gálvez‐Martín, P., & Marchal, J. A. (2022) · Medicinal Research Reviews · doi:10.1002/med.21914 · Cited by 18
3D Bioprinting for Tumor Metastasis Research
Lin, M., Tang, M., Duan, W., Xia, S., Liu, W., & Wang, Q. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c00239 · Cited by 19
Analyzing the impact of metabolism on immune cells in tumor microenvironment to promote the development of immunotherapy
Long, Y., Shi, H., He, Y., & Qi, X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1307228 · Cited by 18
Patient-derived organoid co-culture systems as next-generation models for bladder cancer stem cell research
Yang, R., Wang, S., Li, Z., Yin, C., Huang, W., & Huang, W. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217793 · Cited by 19
Assessment and process optimization of high throughput biofabrication of immunocompetent breast cancer model for drug screening applications
Shukla, P., Bera, A. K., Ghosh, A. K., Kiranmai, G., & Pati, F. (2024) · Biofabrication · doi:10.1088/1758-5090/ad586b · Cited by 16
Establishment of advanced tumor organoids with emerging innovative technologies
Mao, Y., & Hu, H. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217122 · Cited by 18
Microfluidic devices: The application in TME modeling and the potential in immunotherapy optimization
Li, Y., Fan, H., Ding, J., Xu, J., Liu, C., & Wang, H. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.969723 · Cited by 16
Harnessing Tissue Engineering Tools to Interrogate Host-Microbiota Crosstalk in Cancer
Udayasuryan, B., Nguyen, T. T. D., Slade, D. J., & Verbridge, S. S. (2020) · iScience · doi:10.1016/j.isci.2020.101878 · Cited by 15
Tumor spheroid-based microtumor models for preclinical evaluation of anticancer nanomedicines
Khawar, I. A., Ghosh, T., Park, J. K., & Kuh, H. (2021) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-021-00534-y · Cited by 15
Ex vivo modeling of precision immuno-oncology responses in lung cancer
Alsaed, B., Smolander, J., Laitinen, H. K., Lin, L., Bobik, N., Lahtinen, L., Räsänen, M., Jansouz, S., Peltonen, K., Jokinen, E., et al. (2024) · Science Advances · doi:10.1126/sciadv.adq6830 · Cited by 16
Deciphering the Mechanics of Cancer Spheroid Growth in 3D Environments through Microfluidics Driven Mechanical Actuation
Aung, A., Davey, S. K., Theprungsirikul, J., Kumar, V., & Varghese, S. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202201842 · Cited by 16
Self-citation
Engineering models of head and neck and oral cancers on-a-chip
Sousa, M. G. D. C., Vignolo, S. M., França, C. M., Mereness, J. A., Fraga, M. A. A., Silva‐Sousa, A. C., Benoit, D. S. W., & Bertassoni, L. E. (2024) · Biomicrofluidics · doi:10.1063/5.0186722 · Cited by 14
Engineering stromal heterogeneity in cancer
Tang, L. J. W., Zaseela, A., Toh, C. C. M., Adine, C., Aydar, A. O., Iyer, N. G., & Fong, E. L. S. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.05.027 · Cited by 15
Microphysiological systems as models for immunologically ‘cold’ tumors
Gaebler, D., Hachey, S. J., & Hughes, C. C. W. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1389012 · Cited by 14
Immune‐Infiltrated Cancer Spheroid Model with Vascular Recirculation Reveals Temporally Dependent and Tissue‐Specific Macrophage Recruitment
Zhang, F., Jozani, K. A., Chakravarty, A., Lin, D. S. Y., Hollinger, A., Rajasekar, S., & Zhang, B. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202402946 · Cited by 14
Cancer-on-chip technology: current applications in major cancer types, challenges and future prospects
Baka, Z., Stiefel, M., Figarol, A., Godier, C., Mallick, A., Joubert, O., Ashammakhi, N. A., Gaffet, É., & Alem, H. (2022) · Progress in Biomedical Engineering · doi:10.1088/2516-1091/ac8259 · Cited by 13
Microfluidic Biosensor-Based Devices for Rapid Diagnosis and Effective Anti-cancer Therapeutic Monitoring for Breast Cancer Metastasis
Sudhakaran, S. V., & Rath, S. N. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-04039-9_13 · Cited by 13
Flow‐Induced Vascular Remodeling on‐Chip: Implications for Anti‐VEGF Therapy
Mirzapourshafiyi, F., Huber, E., Karr, L., Tong, J., Bausch, A. R., Simmel, F. C., & Alim, K. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202501416 · Cited by 14
Spatial -omics technologies: the new enterprise in 3D breast cancer models
Pierantoni, L., Reis, R. L., Silva‐Correia, J., Oliveira, J. M., & Heavey, S. (2023) · Trends in biotechnology · doi:10.1016/j.tibtech.2023.07.003 · Cited by 12
Targeted Cancer Therapy‐on‐A‐Chip
Abed, H., Radha, R., Anjum, S., Paul, V., AlSawaftah, N., Pitt, W. G., Ashammakhi, N. A., & Husseini, G. A. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202400833 · Cited by 12
Spheroid-Hydrogel-Integrated Biomimetic System: A New Frontier in Advanced Three-Dimensional Cell Culture Technology
Yoo, S., & Lee, H. J. (2024) · Cells Tissues Organs · doi:10.1159/000541416 · Cited by 13
Advances and Challenges in Human 3D Solid Tumor Models
Natesh, N. R., & Varghese, S. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202419912 · Cited by 13
Self-citation
Applications and evolution of 3D cancer-immune cell models
Co, I. L., Fomina, A., Nurse, M., & McGuigan, A. P. (2024) · Trends in biotechnology · doi:10.1016/j.tibtech.2024.06.008 · Cited by 10
Recapitulating the Cancer‐Immunity Cycle on a Chip
Lee, Y., Min, J., Kim, S., Park, W., Ko, J., & Jeon, N. L. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202401927 · Cited by 10
Ex Vivo Evaluation of Combination Immunotherapy Using Tumor‐Microenvironment‐on‐Chip
Mu, H., Lin, C., Chu, L., Lin, Y., Li, J., Liu, C., Huang, H., Cheng, S., Lee, T., Lee, H. M., et al. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202302268 · Cited by 9
In Vitro Assessment of Thermo‐Responsive Scaffold as a 3D Synthetic Matrix for CAR‐T Potency Testing Against Glioblastoma Spheroids
Lizana‐Vasquez, G. D., Ramasubramanian, S., Davarzani, A., Cappabianca, D., Saha, K., Karumbaiah, L., & Torres‐Lugo, M. (2024) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37823 · Cited by 11
Microphysiological Systems in Cancer Research: Advancing Immunotherapy through Tumor Microenvironment‐Integrated Organ‐On‐Chip Models
Moresi, F., Noto, F., Vasudevan, J., Bisteau, X., Adriani, G., & Pavesi, A. (2025) · Advanced Therapeutics · doi:10.1002/adtp.202500098 · Cited by 10
Immune microenvironment dynamics of HER2 overexpressing breast cancer under dual anti-HER2 blockade
Batalha, S., Gomes, C. M., & Brito, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1267621 · Cited by 13
Imaging‐Based Efficacy Evaluation of Cancer Immunotherapy in Engineered Tumor Platforms and Tumor Organoids
Kim, S., Yun, S., Doh, J., & Kim, H. N. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202400475 · Cited by 10
Advancing Tumor Microenvironment Research by Combining Organs-on-Chips and Biosensors
Calejo, I., Heinrich, M. A., Zambito, G., Mezzanotte, L., Prakash, J., & Teixeira, L. M. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-04039-9_7 · Cited by 9

Authors: Aung, A., Kumar, V., Theprungsirikul, J., Davey, S. K., & Varghese, S.
Affiliations: University of California San Diego (US)
Duke University (US)
Corresponding author: Varghese, Shyni
ORCID: Aung, Aereas
Kumar, Vardhman
Theprungsirikul, Jomkuan
Varghese, Shyni
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2020-01-15
Volume: 80
Issue: 2
Pages: 263-275
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-19-0342
PMC: PMC8545579
OpenAlex: W2991421324
Cited by: 146
References: 50
Citations by year: 2026: 12 · 2025: 21 · 2024: 27 · 2023: 22 · 2022: 28 · 2021: 22 · 2020: 14
FWCI: 5.63
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: NIH NHLBI (T32 HL 105373)
Topics: Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
Keywords: tumor-on-a-chip, breast cancer, T cell recruitment, tumor microenvironment, tumor-immune interactions, monocytes, endothelial cells, gelatin hydrogel, chemokines, hypoxia, tumor spheroids, endothelial permeability, tumor cell migration
MeSH terms: Proof of Concept Study, Breast Neoplasms, Cell Communication, Feasibility Studies, Female, Humans, Lymphocyte Activation, Monocytes, T-Lymphocytes, Cell Hypoxia, Spheroids, Cellular, Chemokines, Cell Culture Techniques, Hydrogels, Cell Line, Tumor, Lab-On-A-Chip Devices, Tumor Microenvironment, Cell Engineering, Human Umbilical Vein Endothelial Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks