University of Saskatchewan, College of Dentistry, 105 Wiggins Road, Saskatoon, SK, Canada.
University of Saskatchewan, College of Dentistry, 105 Wiggins Road, Saskatoon, SK, Canada.
Matrix Biol. 2023 May;119:125-140. doi: 10.1016/j.matbio.2023.04.002. Epub 2023 Apr 18.
Previously, impaired responses to immunotherapy in cancer had been attributed mainly to inherent tumor characteristics (tumor cell intrinsic factors) such as low immunogenicity, (low) mutational burden, weak host immune system, etc. However, mapping the responses of immunotherapeutic regimes in clinical trials for different types of cancer has pointed towards an obvious commonality - that tumors with a rich fibrotic stroma respond poorly or not at all. This has prompted a harder look on tumor cell extrinsic factors such as the surrounding tumor microenvironment (TME), and specifically, the fibrotic stroma as a potential enabler of immunotherapy failure. Indeed, the role of cancer-associated fibrosis in impeding efficacy of immunotherapy is now well-established. In fact, recent studies reveal a complex interconnection between fibrosis and treatment efficacy. Accordingly, in this review we provide a general overview of what a tumor associated fibrotic reaction is and how it interacts with the members of immune system that are frequently seen to be modulated in a failed immunotherapeutic regime.
先前，癌症免疫疗法反应受损主要归因于固有肿瘤特征（肿瘤细胞内在因素），如低免疫原性、（低）突变负担、弱宿主免疫系统等。然而，对不同类型癌症临床试验中免疫治疗方案反应的映射指出了一个明显的共性——富含纤维化基质的肿瘤反应不佳或根本没有反应。这促使人们更加关注肿瘤细胞外在因素，如周围肿瘤微环境（TME），特别是纤维化基质，因为它可能是免疫治疗失败的一个促成因素。事实上，癌症相关纤维化在阻碍免疫疗法疗效方面的作用现在已经得到了很好的证实。事实上，最近的研究揭示了纤维化与治疗疗效之间的复杂联系。因此，在这篇综述中，我们提供了一个关于肿瘤相关纤维化反应是什么以及它如何与免疫系统成员相互作用的概述，免疫系统成员在免疫治疗失败的情况下经常被观察到发生调节。
