Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and therapeutic options for advanced HCC are limited. Here, we observe that intestinal dysbiosis affects antitumor immune surveillance and drives liver disease progression towards cancer. Dysbiotic microbiota, as seen in Nlrp6(-/-) mice, induces a Toll-like receptor 4 dependent expansion of hepatic monocytic myeloid-derived suppressor cells (mMDSC) and suppression of T-cell abundance. This phenotype is transmissible via fecal microbiota transfer and reversible upon antibiotic treatment, pointing to the high plasticity of the tumor microenvironment. While loss of Akkermansia muciniphila correlates with mMDSC abundance, its reintroduction restores intestinal barrier function and strongly reduces liver inflammation and fibrosis. Cirrhosis patients display increased bacterial abundance in hepatic tissue, which induces pronounced transcriptional changes, including activation of fibro-inflammatory pathways as well as circuits mediating cancer immunosuppression. This study demonstrates that gut microbiota closely shapes the hepatic inflammatory microenvironment opening approaches for cancer prevention and therapy. Steatohepatitis is a chronic hepatic inflammation associated with increased risk of hepatocellular carcinoma progression. Here the authors show that intestinal dysbiosis in mice lacking the inflammasome sensor molecule NLRP6 aggravates steatohepatitis and accelerates liver cancer progression, a process that can be delayed by antibiotic treatment.Peer reviewe

Z-pinch plasma lens focusing of a heavy-ion beam

For the first time a heavy-ion beam was focused using a z-pinch plasma lens. The diameter of an incident, parallel, 460-MeV argon-ion beam was reduced from 8 mm (FWHM) to 2 mm within 230 mm downstream of the plasma. Inside a cylindrically symmetric plasma column a high-gradient, azimuthal magnetic field is produced during a z-pinch discharge. For axially moving, high-energy charged particles this field configuration provides strong, first-order focusing simultaneously in both transversal planes. The measured spot size agrees with numerical calculations taking into account the finite beam emittance, and charge exchange as well as energy-loss processes contributing to aberrations