Could intratumoural microbiota be key to unlocking treatment responses in hepatocellular carcinoma?

Abstract

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.