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An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment
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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.
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“The results showed greater T cell in fi ltration 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].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [71]
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“T cell recruitment to tumor spheroids was shown to be increased in the presence of monocytes due to their increased chemokine expression [45].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [45]
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Metadata
- 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
- Venue
- Cancer Research
- Published
- 2020-01-15
- Volume
- 80
- Issue
- 2
- Pages
- 263-275
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- 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
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