Engineered Tumor-Immune Microenvironment On A Chip to Study T Cell-Macrophage Interaction in Breast Cancer Progression.

Autor: Manoharan TJM; School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA., Ravi K; School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA., Suresh AP; School for Engineering of Matter, Transport and Energy (SEMTE), Arizona State University, Tempe, AZ, 85287, USA.; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA., Acharya AP; School for Engineering of Matter, Transport and Energy (SEMTE), Arizona State University, Tempe, AZ, 85287, USA.; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA., Nikkhah M; School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA.; Biodesign Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Jun; Vol. 13 (14), pp. e2303658. Date of Electronic Publication: 2024 Feb 25.
DOI: 10.1002/adhm.202303658
Abstrakt: Evolving knowledge about the tumor-immune microenvironment (TIME) is driving innovation in designing novel therapies against hard-to-treat breast cancer. Targeting the immune components of TIME has emerged as a promising approach for cancer therapy. While recent immunotherapies aim at restoring antitumor immunity, counteracting tumor escape remains challenging. Hence there is a pressing need to better understand the complex tumor-immune crosstalk within TIME. Considering this imperative, this study aims at investigating the crosstalk between the two abundant immune cell populations within the breast TIME-macrophages and T cells, in driving tumor progression using an organotypic 3D in vitro tumor-on-a-chip (TOC) model. The TOC features distinct yet interconnected organotypic tumor and stromal entities. This triculture platform mimics the complex TIME, embedding the two immune populations in a suitable 3D matrix. Analysis of invasion, morphometric measurements, and flow cytometry results underscores the substantial contribution of macrophages to tumor progression, while the presence of T cells is associated with a deceleration in the migratory behavior of both cancer cells and macrophages. Furthermore, cytokine analyses reveal significant upregulation of leptin and RANTES (regulated on activation, normal T Cell expressed and secreted) in triculture. Overall, this study highlights the complexity of TIME and the critical role of immune cells in cancer progression.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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