2023年5月10日 - 荷兰MIMETAS科学家们发展并表征了一种胰腺导管腺癌（PDAC）模型，并利用它来研究内皮细胞和肿瘤基质在免疫细胞迁移中的作用。

PDAC是最具侵袭性的癌症之一，其生存率非常低。虽然免疫疗法已成为几种癌症类型的有前景的治疗选项，但对PDAC开发有效的免疫疗法一直充满挑战。这主要是由PDAC特征的免疫抑制性肿瘤微环境（TME）所致，尤其是基质分泌因子、缺氧、肿瘤纤维化和血管异常往往对化疗和免疫细胞浸润到肿瘤中心构成阻碍。免疫细胞必须首先离开靠近肿瘤的血管，然后渗透基质才能到达组织并发挥抗肿瘤效应，这是一个通常在PDAC患者中受阻的复杂过程。

借助细胞和微流体技术的进步，人们现在可以通过体外系统来模拟TME的生物学特性，进而在肿瘤免疫和肿瘤对靶向治疗反应的研究中取得进展。特别是，器官芯片技术能够进行3D培养多种类型的细胞，实现细胞与细胞、细胞与基质的互动以及流体的流动。在这项研究中，MIMETAS科学家们利用OrganoPlate产品构建了一个包括内皮管、胰腺星状细胞（PSCs）和PDAC类器官的3D PDAC-on-a-chip模型。此模型有助于研究TME对免疫细胞招募的影响，以及其阻止免疫细胞与胰腺癌细胞交互的效应。他们发现，基质细胞形成一个物理障碍，部分屏蔽癌细胞防止免疫细胞的迁移，同时也形成了一个生化微环境，这似乎能够吸引并影响免疫细胞的分布。此外，通过Halofuginone针对基质进行靶向后，免疫细胞的浸润程度增加。

这种模型的开发是PDAC和免疫细胞研究的重大突破，将有助于我们理解影响免疫细胞招募和分布的细胞间相互作用，并加快发现治疗这种免疫抑制癌症的新策略。

英文原文：
The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model

Leiden, May 10, 2023 – MIMETAS scientists develop and characterize a pancreatic ductal adenocarcinoma (PDAC) model and applied it to study the role of the endothelium and the stroma in immune cell migration.

PDAC is one of the most aggressive forms of cancer and has a very low survival rate. Immunotherapy has emerged as a promising treatment option for several types of cancer, but it has been challenging to develop effective immunotherapies for PDAC. This is mostly explained by the immunosuppressive tumor microenvironment (TME) that characterizes PDAC; specifically, stroma-secreted factors, hypoxia, desmoplasia and abnormal vasculature most likely provide a barrier for chemotherapy treatment and immune cell infiltration to the tumor core. Immune cells must first exit a blood vessel near the tumor and infiltrate the stroma to reach the tissue and exert antitumor responses. – a complex process that is often hindered in PDAC patients.

Advances in cellular and microfluidic technologies that allow in vitro systems to emulate in vivo biology of the TME have enabled progress in the study of tumor immunity of this cancer and its response to targeting. Organ-on-chip systems, in particular, enable 3D cultivation of multiple cell types, enabling cell-cell interactions, cell-matrix interactions, and flow. In this study, MIMETAS scientists established a 3D PDAC-on-a-chip model comprising an endothelial tube, pancreatic stellate cells (PSCs), and PDAC organoids. This model facilitated the investigation of the role of the TME on immune cell recruitment and its effect on preventing their interaction with pancreatic cancer cells. They found that stromal cells form a physical barrier, partly shielding the cancer cells from migrating immune cells, as well as a biochemical microenvironment, that seems to attract and influence immune cell distribution. In addition, stromal targeting by Halofuginone led to an increase in immune cell infiltration.

The development of this model is a significant breakthrough in the study of PDAC and immune cells and will support the understanding of the cellular interplay influencing the recruitment and distribution of immune cells and enhance the discovery of new strategies to treat this immunosuppressive cancer.

论文链接：https://www.frontiersin.org/articles/10.3389/fimmu.2023.1155085/full
原文链接：https://www.frontiersin.org/articles/10.3389/fimmu.2023.1155085/full
 

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