Potential tactics with certain gut microbiota for the treatment of unresectable hepatocellular carcinoma

Explor Target Antitumor Ther. 2023;4(4):556-568. doi: 10.37349/etat.2023.00152. Epub 2023 Aug 24.

Abstract

Hepatocellular carcinoma (HCC) constitutes an extremely malignant form of primary liver cancer. Intricate connections linking to the immune system might be associated with the pathogenesis of HCC. Meanwhile, immunotherapy with immune checkpoint inhibitors has been established to be a favorable therapeutic possibility for advanced HCC. Although curative opportunities for advanced HCC are restricted, the immune checkpoint immunotherapy has developed as the main choice for treating HCC. However, patients with metabolic-associated fatty liver disease (MAFLD)-linked HCC might be less likely to benefit from the immunotherapy alone. The limitation of the effect of the immunotherapy might be owing to the impaired T cell activation in MAFLD patients, which could be well explained by a dysfunctional gut-liver axis. Gut microbiota and their metabolites including several bile acids could contribute to modulating the responses of the immune checkpoint immunotherapy. Roles of gut microbiota in the development of cancers have expected great interest in the latest studies. Here, an interplay between the gut and liver has been presented, which might suggest to affect the efficacy of immune checkpoint immunotherapy against HCC.

Keywords: Hepatocellular carcinoma; T helper 17 cells; gut microbiota; immune checkpoint inhibitors; metabolic-associated fatty liver disease; non-alcoholic fatty liver disease; probiotics; regulatory T cells.