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Macroautophagy/autophagy is an important catabolic process mediating cellular homeostasis and plays critical roles in cancer development. Whereas autophagy has been widely studied in various pathological models, little is known about the distribution, clinical significance and regulatory mechanism of this process in human hepatocellular carcinoma (HCC). In the present study, we found that tumor tissues exhibited significantly increased levels of autophagy compared with non-tumor tissues, and cancer cells with higher levels of autophagy were predominantly enriched in the invading edge regions of human HCC. Increased MAP1LC3B/LC3B expression in the invading edge regions was significantly correlated with a higher density of closely located monocytes, and TNF and IL1B derived from tumor-activated monocytes synergistically induced cancer cell autophagy in the invading edge regions of HCC. Monocyte-elicited autophagy induced the epithelial-mesenchymal transition (EMT) of cancer cells and promoted tumor metastasis by activating the NFKB-SNAI1 signaling pathway. Moreover, the increase of LC3B cancer cells in the invading edge areas was associated with high mortality and reduced survival of patients with HCC. These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction.

Neutrophils constitute a major component in human hepatocellular carcinoma (HCC) and can facilitate disease progression via poorly understood mechanisms. Here, we show that neutrophil extracellular traps (NETs) formation was increased in human HCC tumor tissues than in paired non-tumor liver tissues. Mechanism study revealed that tumor-induced metabolic switch toward glycolysis and pentose phosphate pathway in tumor infiltrating neutrophils promoted NETs formation in a reactive oxygen species dependent-manner. NETs subsequently induced the migration of cancer cells and down-regulation of tight junction molecules on adjacent endothelial cells, thus facilitating tumor intravasation and metastasis. Accordingly, NETs depletion could inhibit tumor metastasis in mice in vivo , and the infiltration levels of NETs-releasing neutrophils were negatively associated with patient survival and positively correlated with tumor metastasis potential of HCC patients. Our results unveiled a pro-metastatic role of NETs in the milieu of human HCC, and pointed to the importance of metabolic reprogramming in shaping their characteristics, thus providing an applicable efficient target for anti-cancer therapies.

Senecavirus A (SVA), previously known as Seneca Valley virus, is classified into the genus Senecavirus in the family Picornaviridae . This virus can cause vesicular disease and epidemic transient neonatal losses in swine. Typical clinical signs include vesicular and/or ulcerative lesions on the snout, oral mucosa, coronary bands and hooves. SVA emerged in Guangdong Province of China in 2015, and thereafter gradually spread into other provinces, autonomous regions and municipalities (P.A.M.s). Nowadays more than half of the P.A.M.s have been affected by SVA, and asymptomatic infection has occurred in some areas. The phylogenetic analysis shows that China isolates are clustered into five genetic branches, implying a fast evolutionary speed since SVA emergence in 2015. This review presented current knowledge concerning SVA infection in China, including its history, epidemiology, evolutionary characteristics, diagnostics and vaccines.