A New Preventive Therapeutic Strategy for Liver Cancer

Liver cancer is the second most common cause of cancer‐related death with difficulties of immune therapeutics. When administered at pre‐cancer stages, the immunostimulatory synthetic double‐stranded RNA (dsRNA), polyinosinic‐polycytidylic acid (pIC) robustly induced tumor remission with no cytotoxic effect in either chemically‐induced or phosphatase and tensin homolog (PTEN) knockout‐induced liver cancer in mice by boosting multiple anti‐tumor immune activities, including natural killer (NK) cells and reprogramming of macrophage polarization. In contrast, a potent anti‐tumor dsRNA, in late stages of PTEN loss‐associated hepatosteatosis markedly increased tumor burden. Injection of dsRNA stimulated macrophage type II and regulatory T cells in PTEN‐knockout mice without affecting lipid accumulation, expression of α‐smooth muscle actin (α‐SMA) and cholangiocyte expansion at late stages. This study provides a new strategy for approaching immune therapeutics for the large population of at‐risk and liver cancer patients at different stages. Support or Funding Information We thank Drs. D. Brenner, J Bui, M. Kaplan, M. Karin, T. Kisseleva, B. Schnabl and colleagues in the Feng lab for helpful discussion, critical reading of the manuscript or reagents. This work was supported by R01CA176012 and R01CA188506 to (G.S.F.), and P30DK063491, and JDRF 2‐SRA‐2016‐306‐S‐B (to W.F.). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .