PDF(Pubmed)
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.
摘要：
关于肿瘤免疫微环境（TIME）的不断发展的知识正在推动设计针对难以治疗的乳腺癌的新疗法的创新。靶向TIME的免疫成分已经成为一种有希望的癌症治疗方法。虽然最近的免疫疗法旨在恢复抗肿瘤免疫力，对抗肿瘤逃逸仍然具有挑战性。因此，迫切需要更好地理解TIME中复杂的肿瘤-免疫串扰。考虑到这一必要性，这项研究旨在研究乳腺TIME-巨噬细胞和T细胞内两种丰富的免疫细胞群之间的串扰，使用器官型3D体外芯片上肿瘤（TOC）模型驱动肿瘤进展。TOC具有独特但相互关联的器官型肿瘤和基质实体。我们的三文化平台模仿了复杂的时间，将两个免疫群体嵌入合适的3D矩阵中。入侵分析,形态测量，流式细胞术结果强调了巨噬细胞对肿瘤进展的实质性贡献，而T细胞的存在与癌细胞和巨噬细胞迁移行为的减速有关。此外，细胞因子分析显示，在培养过程中，瘦素和RANTES显著上调。总的来说,这项研究强调了时间的复杂性和免疫细胞在癌症进展中的关键作用.本文受版权保护。保留所有权利。
