造血细胞源性外泌体在癌症发展和治疗中的应用:从基础科学到临床实践。
Haematopoietic cell-derived exosomes in cancer development and therapeutics: From basic science to clinical practice.
发表日期:2023 Oct
作者:
Wen-Chun Lin, You-Tong Lin, Hui-Ching Chao, Yen-Yu Lin, Wei-Lun Hwang
来源:
Clinical and Translational Medicine
摘要:
肿瘤微环境(TME)是一个专门的生态位,涉及癌细胞和各种宿主细胞之间的细胞间通讯。在宿主细胞中,TME 内免疫细胞的数量和质量在癌症的发展和管理中发挥着至关重要的作用。由一系列肿瘤-宿主相互作用(包括产生免疫抑制细胞因子和招募调节性宿主免疫细胞)建立的免疫抑制性所谓“冷”TME,与治疗耐药和较差的临床结果相关。针对冷 TME,包括免疫检查点阻断疗法和过继性 T 细胞移植。一种有前途但较少探索的治疗策略涉及靶向 TME 相关的外泌体。外泌体是纳米大小的细胞外囊泡,可将物质从供体细胞转移到受体细胞。这些颗粒可以对受体细胞进行重新编程并调节 TME。特别是,已知来自造血细胞的外泌体在特定条件下促进或抑制癌症进展。了解造血细胞分泌的外泌体的作用可能会促进用于个性化癌症治疗的治疗性外泌体(tExos)的开发。然而,基于外泌体的疗法的开发面临着独特的挑战,包括外泌体的可扩展生产、纯化、储存和递送以及控制批次变化。目前正在进行临床试验来验证 tExos 的安全性、可行性、可用性和有效性。这篇综述总结了我们对造血细胞分泌的外泌体如何调节 TME 和抗肿瘤免疫的理解,并强调了基于造血细胞分泌的外泌体目前面临的挑战和解决方案疗法。© 2023 作者。约翰·威利出版的《临床与转化医学》
The tumour microenvironment (TME) is a specialised niche involving intercellular communication among cancer cells and various host cells. Among the host cells, the quantity and quality of immune cells within the TME play essential roles in cancer development and management. The immunologically suppressive, so-called 'cold' TME established by a series of tumour-host interactions, including generating immunosuppressive cytokines and recruiting regulatory host immune cells, is associated with resistance to therapies and worse clinical outcomes.Various therapeutic approaches have been used to target the cold TME, including immune checkpoint blockade therapy and adoptive T-cell transfer. A promising, less explored therapeutic strategy involves targeting TME-associated exosomes. Exosomes are nanometer-sized, extracellular vesicles that transfer material from donor to recipient cells. These particles can reprogram the recipient cells and modulate the TME. In particular, exosomes from haematopoietic cells are known to promote or suppress cancer progression under specific conditions. Understanding the effects of haematopoietic cell-secreted exosomes may foster the development of therapeutic exosomes (tExos) for personalised cancer treatment. However, the development of exosome-based therapies has unique challenges, including scalable production, purification, storage and delivery of exosomes and controlling batch variations. Clinical trials are being conducted to verify the safety, feasibility, availability and efficacy of tExos.This review summarises our understanding of how haematopoietic cell-secreted exosomes regulate the TME and antitumour immunity and highlights present challenges and solutions for haematopoietic cell-derived exosome-based therapies.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.