Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Cell Biochem Funct. 2024 Jul;42(5):e4098. doi: 10.1002/cbf.4098.
Hepatocellular carcinoma (HCC) presents a considerable global health burden due to its late diagnosis and high morbidity. The liver's specific anatomical and physiological features expose it to various antigens, requiring precise immune regulation. To the best of our knowledge, this is the first time that a comprehensive overview of the interactions between the immune system and gut microbiota in the development of HCC, as well as the relevant therapeutic approaches are discussed. Dysregulation of immune compartments within the liver microenvironment drives HCC pathogenesis, characterized by elevated regulatory cells such as regulatory T cells (Tregs), myeloid-derived suppressor cells, and M2 macrophages as well as suppressive molecules, alongside reduced number of effector cells like T cells, natural killer cells, and M1 macrophages. Dysbiosis of gut microbiota also contributes to HCC by disrupting intestinal barrier integrity and triggering overactivated immune responses. Immunotherapy approaches, particularly immune checkpoint inhibitors, have exhibited promise in HCC management, yet adoptive cell therapy and cancer vaccination research are in the early steps with relatively less favorable outcomes. Further understanding of immune dysregulation, gut microbiota involvement, and therapeutic combination strategies are essential for advancing precision immunotherapy in HCC.
肝细胞癌 (HCC) 由于诊断较晚和发病率高，给全球健康带来了相当大的负担。肝脏的特殊解剖和生理特征使其暴露于各种抗原之下，需要精确的免疫调节。据我们所知，这是第一次全面探讨免疫系统与肠道微生物群在 HCC 发展中的相互作用，以及相关的治疗方法。肝脏微环境中免疫细胞的失调会导致 HCC 的发病机制，其特征是调节性 T 细胞 (Tregs)、髓源性抑制细胞和 M2 巨噬细胞等调节性细胞以及抑制性分子的水平升高，而 T 细胞、自然杀伤细胞和 M1 巨噬细胞等效应细胞的数量减少。肠道微生物群的失调也会通过破坏肠道屏障完整性和引发过度激活的免疫反应而导致 HCC。免疫疗法，特别是免疫检查点抑制剂，在 HCC 的治疗中显示出了一定的前景，但过继细胞疗法和癌症疫苗研究仍处于早期阶段，结果相对不太理想。进一步了解免疫失调、肠道微生物群的参与以及治疗联合策略，对于推进 HCC 的精准免疫治疗至关重要。
