CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Haematopoietic cell-derived exosomes in cancer development and therapeutics: From basic science to clinical practice.
Haematopoietic cell-derived exosomes in cancer development and therapeutics: From basic science to clinical practice.
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本综述总结了我们对造血细胞分泌的外泌体如何调控 TME 和抗肿瘤免疫的理解,并强调了基于造血细胞来源外泌体疗法当前面临的挑战和解决方案。
肿瘤微环境(TME)是一个特殊的生态位,涉及癌细胞与多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发生和治疗中发挥重要作用。由一系列肿瘤-宿主相互作用(包括产生免疫抑制性细胞因子和招募调节性宿主免疫细胞)所建立的免疫抑制性、即所谓的“冷”TME,与治疗耐药和较差的临床结局相关。正文:多种治疗策略已被用于靶向冷TME,包括免疫检查点阻断治疗和过继性T细胞转移。一种有前景但探索较少的治疗策略是靶向TME相关外泌体。外泌体是纳米级细胞外囊泡,可将物质从供体细胞转移至受体细胞。这些颗粒能够重编程受体细胞并调节TME。特别是,已知来自造血细胞的外泌体在特定条件下可促进或抑制癌症进展。理解造血细胞分泌的外泌体的作用可能促进用于个性化癌症治疗的治疗性外泌体(tExos)的开发。然而,基于外泌体的疗法开发面临独特的挑战,包括外泌体的可规模化生产、纯化、储存和递送,以及控制批次差异。目前正在进行临床试验,以验证tExos的安全性、可行性、可获得性和疗效。
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. MAIN BODY: 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.
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