Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao PR China; Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, PR China; Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, PR China.
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, PR China; Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, PR China.
Biomed Pharmacother. 2024 Apr;173:116409. doi: 10.1016/j.biopha.2024.116409. Epub 2024 Mar 8.
Hepatocellular carcinoma (HCC) is a malignant liver cancer characterized by aggressive progression, unfavorable prognosis, and an increasing global health burden. Therapies that precisely target immunological checkpoints and immune cells have gained significant attention as possible therapeutics in recent years. In truth, the efficacy of immunotherapy is heavily contingent upon the tumor microenvironment (TME). Recent studies have indicated that exosomes serve as a sophisticated means of communication among biomolecules, executing an essential part in the TME of immune suppression. Exosomal non-coding RNAs (ncRNAs) can induce the activation of tumor cells and immunosuppressive immune cells that suppress the immune system, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), CD8 T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs). This cell-cell crosstalk triggered by exosomal ncRNAs promotes tumor proliferation and metastasis, angiogenesis, malignant phenotype transformation, and drug resistance. Hence, it is imperative to comprehend how exosomal ncRNAs regulate tumor cells or immune cells within the TME to devise more comprehensive and productive immunotherapy programs. This study discusses the features of exosomal ncRNAs in HCC and how the activation of the exosomes redefines the tumor's immunosuppressive microenvironment, hence facilitating the advancement of HCC. Furthermore, we also explored the potential of exosomal ncRNAs as a viable biological target or natural vehicle for HCC therapy.
肝细胞癌（HCC）是一种恶性肝癌，其具有侵袭性进展、预后不良和全球健康负担不断增加的特点。近年来，精确靶向免疫检查点和免疫细胞的治疗方法作为可能的治疗方法引起了广泛关注。事实上，免疫疗法的疗效在很大程度上取决于肿瘤微环境（TME）。最近的研究表明，外泌体作为生物分子之间复杂的通讯手段，在外泌体免疫抑制微环境中发挥着重要作用。外泌体非编码 RNA（ncRNA）可以诱导肿瘤细胞和抑制免疫系统的免疫抑制性免疫细胞（如癌相关成纤维细胞（CAFs）、肿瘤相关巨噬细胞（TAMs）、肿瘤相关中性粒细胞（TANs）、CD8+T 细胞、调节性 T 细胞（Tregs）和调节性 B 细胞（Bregs））的激活。外泌体 ncRNA 引发的细胞间通讯促进肿瘤增殖和转移、血管生成、恶性表型转化和耐药性。因此，了解外泌体 ncRNA 如何调节 TME 中的肿瘤细胞或免疫细胞以设计更全面和有效的免疫治疗方案至关重要。本研究讨论了 HCC 中外泌体 ncRNA 的特征，以及外泌体的激活如何重新定义肿瘤的免疫抑制微环境，从而促进 HCC 的进展。此外，我们还探讨了外泌体 ncRNA 作为 HCC 治疗的可行生物靶点或天然载体的潜力。
