Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Int Immunopharmacol. 2024 Jul 30;136:112406. doi: 10.1016/j.intimp.2024.112406. Epub 2024 Jun 7.
Tumor-associated macrophages (TAMs) exert profound influences on cancer progression, orchestrating a dynamic interplay within the tumor microenvironment. Recent attention has focused on the role of TAM-derived exosomes, small extracellular vesicles containing bioactive molecules, in mediating this intricate communication. This review comprehensively synthesizes current knowledge, emphasizing the diverse functions of TAM-derived exosomes across various cancer types. The review delves into the impact of TAM-derived exosomes on fundamental cancer hallmarks, elucidating their involvement in promoting cancer cell proliferation, migration, invasion, and apoptosis evasion. By dissecting the molecular cargo encapsulated within these exosomes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and proteins, the review uncovers key regulatory mechanisms governing these effects. Noteworthy miRNAs, such as miR-155, miR-196a-5p, and miR-221-3p, are highlighted for their pivotal roles in mediating TAM-derived exosomal communication and influencing downstream targets. Moreover, the review explores the impact of TAM-derived exosomes on the immune microenvironment, particularly their ability to modulate immune cell function and foster immune evasion. The discussion encompasses the regulation of programmed cell death ligand 1 (PD-L1) expression and subsequent impairment of CD8 + T cell activity, unraveling the immunosuppressive effects of TAM-derived exosomes. With an eye toward clinical implications, the review underscores the potential of TAM-derived exosomes as diagnostic markers and therapeutic targets. Their involvement in cancer progression, metastasis, and therapy resistance positions TAM-derived exosomes as key players in reshaping treatment strategies. Finally, the review outlines future directions, proposing avenues for targeted therapies aimed at disrupting TAM-derived exosomal functions and redefining the tumor microenvironment.
肿瘤相关巨噬细胞(TAMs)对癌症的进展有深远的影响,在肿瘤微环境中协调着动态的相互作用。最近的研究重点是 TAM 衍生的外泌体的作用,这些小的细胞外囊泡包含生物活性分子,在介导这种复杂的通讯中发挥着重要作用。这篇综述全面总结了目前的知识,强调了 TAM 衍生的外泌体在各种癌症类型中的不同功能。该综述深入探讨了 TAM 衍生的外泌体对癌症基本特征的影响,阐明了它们在促进癌细胞增殖、迁移、侵袭和逃避凋亡中的作用。通过剖析这些外泌体中包裹的分子货物,包括 microRNAs (miRNAs)、长链非编码 RNA (lncRNAs) 和蛋白质,该综述揭示了调控这些效应的关键调节机制。值得注意的是,miRNAs,如 miR-155、miR-196a-5p 和 miR-221-3p,因其在介导 TAM 衍生的外泌体通讯和影响下游靶标方面的关键作用而受到关注。此外,该综述还探讨了 TAM 衍生的外泌体对免疫微环境的影响,特别是它们调节免疫细胞功能和促进免疫逃逸的能力。讨论包括程序性细胞死亡配体 1 (PD-L1) 表达的调节及其对 CD8+T 细胞活性的后续影响,揭示了 TAM 衍生的外泌体的免疫抑制作用。着眼于临床意义,该综述强调了 TAM 衍生的外泌体作为诊断标志物和治疗靶点的潜力。它们在癌症进展、转移和治疗耐药性中的作用使 TAM 衍生的外泌体成为重塑治疗策略的关键因素。最后,该综述概述了未来的方向,提出了针对靶向治疗的途径,旨在破坏 TAM 衍生的外泌体功能并重新定义肿瘤微环境。