The effect of type I interferons in preventing breast cancer metastasis to the lung

癌症是全球第二大死因。癌症的问题不在于原发肿瘤，在许多情况下，原发肿瘤可以通过手术切除，而在于癌细胞从原发肿瘤扩散到身体其他部位，并在那里形成继发肿瘤的能力。这被称为转移，通常包括扩散到肺部。有必要了解转移性细胞是如何在肺部接受的，以及如何限制它们的播种和生长，以减少癌症扩散，从而提高癌症患者的生存率。我们发现，通过给予小鼠I型干扰素，可以改变小鼠的肺环境，使其对癌症转移不友好。I型干扰素是一组重要的细胞因子，有助于对抗病毒感染，但也在抗癌免疫反应中发挥作用。我们将研究不同类型的干扰素或干扰素诱导剂如何阻止转移性乳腺癌细胞进入肺部和/或成功地开始在肺部生长。为了解决我们的问题，我们将使用成熟的小鼠肺转移性乳腺肿瘤模型，因为这些类型的研究不可能在人类身上进行。然而，我们还将在健康的人肺组织上测试不同类型的干扰素，以确认小鼠模型的结果，并为未来的转化研究提供信息。该项目将阐明可以限制癌症转移生长的宿主机制，特别是在肺部，并有助于找到未来癌症治疗发展的靶点。

Cancer is the second leading cause of death globally. The problem with cancer is not so much the primary tumour, which in many cases can be surgically removed, but the ability of cancer cells to spread away from that primary tumour and seed themselves in other parts of the body where they establish secondary tumours. This is called metastasis and often involves spread to the lungs. There is a need to understand how metastatic cells are received in the lungs and how their seeding and growth can be restricted to reduce cancer spread and thereby increase cancer patient survival. We have found that the milieu of the lung in mice can be altered to make it hostile to cancer metastases by giving the animals type I interferons, an important group of cytokines that help fight viral infections but also have a role in anti-cancer immune responses. We will investigate how different types of interferons or interferon-inducing agents can stop metastasising breast cancer cells from entering the lungs and/or to successfully start growing in the lung. To address our questions, we will use well-established mouse models of lung metastatic mammary tumours as these type of studies are impossible to do in humans. However, we will also test different types of interferons on healthy human lung tissue to confirm the results from the mouse models and inform for future translational studies. The project will shed light on host mechanisms that can restrict cancer metastatic growth, especially in the lung, and contribute to finding targets for the development of future cancer therapies.