Gut microbiota in hepatic cancer


Gut microbiota in hepatic cancer : Prof. Christian Toso (HUG)

Hepatocellular carcinoma (HCC) is the fifth most frequent cancer in men and the ninth most frequent cancer in women (http://gco.iarc.fr/today/home). It is associated with a high mortality, representing the second cause of cancer-related death worldwide. In Switzerland, 780 individuals are newly diagnosed with HCC every year (https://www.liguecancer.ch/).

Recent observations suggest that the gut-liver axis have an impact on HCC:

(1) De-novo HCC: LPS promotes de novo HCC in mice, and strategies aimed at decreasing the release (antibiotics, germ-free mice) and action (TLR4-mutant mice) of LPS contribute to HCC prevention. Similarly, the administration of probiotics can prevent HCC. In addition, regular exercise (treadmill running 60 min/day) prevents HCC in NASH PTEN-deficient mice.

(2) Recurrent HCC: The gut-liver axis also appears to have an impact on the risk of HCC recurrence after surgery or transplantation. We have demonstrated that strategies aimed at decreasing the release (antibiotics, remote ischemic preconditioning) or the action (TLR4-mutant mice, TLR4 competitive inhibitor) of LPS prevent liver ischemia-reperfusion lesions and HCC engraftment/growth in mice.

(3) Anti-cancer effect of check-point inhibitors: Immune check point inhibitors targeting PD-1 (nivolumab) are a treatment option against HCC. Recent observations on patients with renal cancer suggest that the anti-cancer effect of check-point inhibitors is modulated by the gut microbiota profile. A similar feature could apply to patients with HCC.

These points illustrate the interaction between the gut microbiota and HCC. They will be expended and discussed during the conference.