可重构微尺度分析可深入了解癌症相关成纤维细胞对免疫细胞募集的调节作用。
A reconfigurable microscale assay enables insights into cancer-associated fibroblast modulation of immune cell recruitment.
机构信息
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.
Koch Institute For Integrative Cancer Research, Massachusetts Institute of Technology, MA 02142, USA.
出版信息
Integr Biol (Camb). 2021 Apr 20;13(4):87-97. doi: 10.1093/intbio/zyab004.
Innate immune cell infiltration into neoplastic tissue is the first line of defense against cancer and can play a deterministic role in tumor progression. Here, we describe a series of assays, using a reconfigurable microscale assay platform (i.e. Stacks), which allows the study of immune cell infiltration in vitro with spatiotemporal manipulations. We assembled Stacks assays to investigate tumor-monocyte interactions, re-education of activated macrophages, and neutrophil infiltration. For the first time in vitro, the Stacks infiltration assays reveal that primary tumor-associated fibroblasts from specific patients differ from that associated with the benign region of the prostate in their ability to limit neutrophil infiltration as well as facilitate monocyte adhesion and anti-inflammatory monocyte polarization. These results show that fibroblasts play a regulatory role in immune cell infiltration and that Stacks has the potential to predict individual patients' cancer-immune response.
先天免疫细胞浸润肿瘤组织是抵御癌症的第一道防线，并且可以在肿瘤进展中起决定性作用。在这里，我们描述了一系列使用可重构微尺度分析平台（即 Stack）的检测方法，该平台允许对体外免疫细胞浸润进行时空操作研究。我们组装了 Stack 检测方法来研究肿瘤-单核细胞相互作用、活化巨噬细胞的再教育以及中性粒细胞浸润。首次在体外，Stacks 浸润检测方法显示，来自特定患者的原发性肿瘤相关成纤维细胞与前列腺良性区域相关的成纤维细胞在限制中性粒细胞浸润以及促进单核细胞黏附和抗炎性单核细胞极化的能力上存在差异。这些结果表明成纤维细胞在免疫细胞浸润中发挥调节作用，并且 Stack 具有预测个体患者癌症免疫反应的潜力。
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