NextCure Inc., Beltsville, MD, United States.
Nordic Bioscience A/S, Herlev, Denmark.
Front Immunol. 2023 Aug 17;14:1199513. doi: 10.3389/fimmu.2023.1199513. eCollection 2023.
It has been known for decades that the tumor extracellular matrix (ECM) is dysfunctional leading to loss of tissue architecture and promotion of tumor growth. The altered ECM and tumor fibrogenesis leads to tissue stiffness that act as a physical barrier to immune cell infiltration into the tumor microenvironment (TME). It is becoming increasingly clear that the ECM plays important roles in tumor immune responses. A growing body of data now indicates that ECM components also play a more active role in immune regulation when dysregulated ECM components act as ligands to interact with receptors on immune cells to inhibit immune cell subpopulations in the TME. In addition, immunotherapies such as checkpoint inhibitors that are approved to treat cancer are often hindered by ECM changes. In this review we highlight the ways by which ECM alterations affect and regulate immunity in cancer. More specifically, how collagens and major ECM components, suppress immunity in the complex TME. Finally, we will review how our increased understanding of immune and immunotherapy regulation by the ECM is leading towards novel disruptive strategies to overcome immune suppression.
几十年来，人们已经知道肿瘤细胞外基质（ECM）功能失调会导致组织架构丧失并促进肿瘤生长。改变的 ECM 和肿瘤纤维化导致组织僵硬，成为免疫细胞浸润肿瘤微环境（TME）的物理屏障。越来越明显的是，ECM 在肿瘤免疫反应中发挥着重要作用。越来越多的数据表明，当失调的 ECM 成分作为配体与免疫细胞上的受体相互作用，抑制 TME 中的免疫细胞亚群时，ECM 成分在免疫调节中也起着更积极的作用。此外，已经批准用于治疗癌症的免疫检查点抑制剂等免疫疗法经常受到 ECM 变化的阻碍。在这篇综述中，我们强调了 ECM 改变如何影响和调节癌症中的免疫。更具体地说，胶原和主要 ECM 成分如何在复杂的 TME 中抑制免疫。最后，我们将回顾我们对 ECM 调节免疫和免疫疗法的理解如何导致新的颠覆性策略来克服免疫抑制。
