Xu Ying, Xu Linyue, Chen Qiuyan, Zou Can, Huang Ju, Zhang Limei
Department of Anesthesiology Operating Room, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
School of Sports Medicine and Health, Chengdu Sport University, Chengdu, China.
Front Immunol. 2025 Apr 8;16:1512480. doi: 10.3389/fimmu.2025.1512480. eCollection 2025.
Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, represents a significant cause of cancer-related mortality. While our understanding of its pathogenesis is comparatively comprehensive, the influence of the tumor microenvironment (TME) on its progression warrants additional investigation. Tumor-associated macrophages (TAMs) have significant impacts on cancer cell proliferation, migration, invasion, and immune response, facilitating a complex interaction within the TME. Exosomes, which measure between 30 and 150 nanometers in size, are categorized into small extracellular vesicles, secreted by a wide range of eukaryotic cells. They can transfer biological molecules including proteins, non-coding RNAs, and lipids, which mediates the intercellular communication within the TME. Emerging evidence has revealed that exosomes regulate macrophage polarization, thus impacting cancer progression and immune responses within the TME of HCC. Moreover, TAM-derived exosomes also play crucial roles in malignant transformation, which hold immense potential for cancer therapy. In this review, we elaborate on the crosstalk between exosomes and TAMs within TME during HCC development. Moreover, we delve into the feasible treatment approaches for exosomes in cancer therapy and emphasize the limitations and challenges for the translation of exosomes derived from TAMs into clinical courses for cancer therapy, which may provide new perspectives on further ameliorations of therapeutic regimes based on exosomes to advance their clinical applications.
肝细胞癌（HCC）是原发性肝癌最常见的类型，是癌症相关死亡的一个重要原因。虽然我们对其发病机制的理解相对全面，但肿瘤微环境（TME）对其进展的影响仍需进一步研究。肿瘤相关巨噬细胞（TAM）对癌细胞的增殖、迁移、侵袭和免疫反应有重大影响，促进了TME内的复杂相互作用。外泌体大小在30到150纳米之间，属于小细胞外囊泡，由多种真核细胞分泌。它们可以传递包括蛋白质、非编码RNA和脂质在内的生物分子，介导TME内的细胞间通讯。新出现的证据表明，外泌体调节巨噬细胞极化，从而影响HCC的TME内的癌症进展和免疫反应。此外，TAM衍生的外泌体在恶性转化中也起着关键作用，在癌症治疗中具有巨大潜力。在这篇综述中，我们阐述了HCC发展过程中TME内的外泌体与TAM之间的相互作用。此外，我们深入探讨了外泌体在癌症治疗中的可行治疗方法，并强调了将TAM衍生的外泌体转化为癌症治疗临床方案的局限性和挑战，这可能为进一步改进基于外泌体的治疗方案以推进其临床应用提供新的视角。
