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.

中文翻译：

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一种可重构的微尺度分析可以深入了解癌症相关的成纤维细胞对免疫细胞募集的调节

摘要

先天免疫细胞浸润到肿瘤组织中是抵御癌症的第一道防线，并且可以在肿瘤进展中发挥决定性作用。在这里，我们使用可重新配置的微型分析平台（即 Stacks）描述了一系列分析，该平台允许通过时空操作研究体外免疫细胞浸润。我们组装了 Stacks 分析来研究肿瘤-单核细胞的相互作用、活化巨噬细胞的再教育和中性粒细胞浸润。首次在体外, Stacks 浸润分析表明，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粘附和抗炎单核细胞极化的能力方面有所不同。这些结果表明，成纤维细胞在免疫细胞浸润中起调节作用，并且 Stacks 有可能预测个体患者的癌症免疫反应。