Yu Kin Lam, Shen Sj
School of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Kensington, NSW, Australia.
Microbiome Research Centre, St George and Sutherland Clinical Campuses, UNSW Sydney, Kogarah, NSW, Australia.
Eur J Cancer. 2025 Feb 5;216:115195. doi: 10.1016/j.ejca.2024.115195. Epub 2024 Dec 21.
Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality worldwide. Current treatments include surgery and immunotherapy with variable response. Despite aggressive treatment, disease progression remains the biggest contributor to mortality. Thus, there is an urgent unmet need to improve current treatments through a better understanding of HCC tumourigenesis. The gut microbiota has been intensively examined in the context of HCC, with evidence showing gut modulation has the potential to modulate tumourigenesis and prognosis. In addition, recent literature suggests the presence of an intratumoural microbiota that may exert significant impacts on the development of solid tumours including HCC. By drawing parallels between the gut and hepatic/tumoural microbiota, we explore in the present review how the hepatic microbiota is established, its impact on tumourigenesis, and how modulation of the gut and hepatic microbiota may be key to improving current treatments of HCC. In particular, we highlight key bacteria that have been discovered in HCC tumours, and how they may affect the tumour immune microenvironment and HCC tumourigenesis. We then explore current therapies that target the intratumoural microbiota. With a deeper understanding of how the intratumoural microbiota is established, how different bacteria may be involved in HCC tumourigenesis, and how they can be targeted, we hope to spark future research in validating intratumoural microbiota as an avenue for improving treatment responses in HCC.
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。目前的治疗方法包括手术和免疫疗法，疗效各异。尽管进行了积极治疗，但疾病进展仍然是导致死亡的最大因素。因此，迫切需要通过更好地了解HCC的肿瘤发生机制来改进现有治疗方法。肠道微生物群已在HCC背景下进行了深入研究，有证据表明肠道调节有可能调节肿瘤发生和预后。此外，最近的文献表明肿瘤内存在微生物群，可能对包括HCC在内的实体瘤的发展产生重大影响。通过比较肠道微生物群与肝脏/肿瘤微生物群，我们在本综述中探讨肝脏微生物群是如何形成的，其对肿瘤发生的影响，以及调节肠道和肝脏微生物群如何可能是改善当前HCC治疗的关键。特别是，我们强调了在HCC肿瘤中发现的关键细菌，以及它们如何影响肿瘤免疫微环境和HCC肿瘤发生。然后，我们探讨了目前针对肿瘤内微生物群的疗法。通过更深入地了解肿瘤内微生物群是如何形成的，不同细菌如何参与HCC肿瘤发生，以及如何靶向它们，我们希望激发未来的研究，以验证肿瘤内微生物群作为改善HCC治疗反应的途径。
