肿瘤微环境
免疫系统
癌症研究
巨噬细胞
乳腺癌
癌症
免疫学
生物
医学
内科学
体外
生物化学
作者
T. R. Manoharan,Karthik Ravi,Abhirami P. Suresh,Abhinav P. Acharya,Mehdi Nikkhah
标识
DOI:10.1002/adhm.202303658
摘要
Abstract 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.
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