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

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 aimed 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 featured distinct yet interconnected organotypic tumor and stromal entities. Our tri-culture platform mimicked 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 was associated with a deceleration in the migratory behavior of both cancer cells and macrophages. Furthermore, cytokine analyses revealed significant upregulation of Leptin and RANTES in triculture. Overall, this study highlights the complexity of TIME and the critical role of immune cells in cancer progression. This article is protected by copyright. All rights reserved.