A reconfigurable microscale assay enables insights into cancer-associated fibroblast modulation of immune cell recruitment

可重构微尺度分析可以深入了解癌症相关成纤维细胞对免疫细胞募集的调节

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作者:Jiaquan Yu, Amber Piazza, Sidney Sparks, Laurel E Hind, David J Niles, Patrick N Ingram, Wei Huang, William A Ricke, David F Jarrard, Anna Huttenlocher, Hirak Basu, David J Beebe1

Abstract

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.

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