Oncode Institute and Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
Mol Cancer. 2021 Dec 1;20(1):154. doi: 10.1186/s12943-021-01463-y.
To identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.
为了寻找新的癌症疗法,近年来肿瘤微环境(TME)受到了广泛关注,特别是通过靶向免疫检查点抑制剂(ICIs)取得了临床成功。TME 由多种细胞类型组成,这些细胞嵌入细胞外基质(ECM)中,包括免疫细胞、内皮细胞和癌相关成纤维细胞(CAFs),它们在肿瘤进展过程中与癌细胞和彼此之间进行交流。CAFs 是 TME 中一种主要的异质细胞类型,在控制癌细胞浸润和转移、免疫逃逸、血管生成和化疗耐药方面发挥着关键作用。CAFs 通过重塑 ECM 并分泌可溶性因子和细胞外囊泡来发挥其作用。外泌体是细胞外囊泡(EVs)的一种亚型,其中包含各种生物分子,如核酸、脂质和蛋白质。外泌体中的生物分子可以从一个细胞传递到另一个细胞,并由此影响接收细胞的行为。由于外泌体也存在于循环中,因此可以将其内容物作为癌症患者诊断和预后的生物标志物进行探索。在这篇综述中,我们集中讨论了 CAFs 衍生的外泌体在 CAFs 与癌细胞和 TME 中的其他细胞之间的通讯中的作用。首先,我们介绍了 CAFs 在肿瘤发生中的多种作用。此后,我们讨论了 CAFs 与癌细胞相互作用以及与 TME 中的其他细胞相互作用的方式,并特别关注外泌体的作用。然后,我们详细阐述了 CAFs 衍生的外泌体促进癌症进展的机制,以及外泌体的临床影响。最后,我们讨论了外泌体值得进一步研究的方面,包括对免疫检查点抑制剂阻断治疗更有效的新兴见解。
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