Favorable prognostic role of IL-26 in HCC patients associated with JAK-STAT3-dependent autophagy

Abstract Interleukin-26 (IL-26), a recently identified cytokine of the IL-20 subfamily, plays an important role in the regulation of host defense and inflammatory diseases. However, whether the role of IL-26 in the progression of hepatocellular carcinoma (HCC) occurs via autophagy remains unclear. Here, we investigated the IL-26 levels in the blood and tissues of subjects, its possible cellular source and its relationship with the prognosis of HCC patients. We also explored the mechanisms by which different pathophysiological levels of IL-26 affect the outcomes of patients; these studies were conducted only in vitro due to the lack of IL-26 gene expression in rodents. We found that IL-26 was highly expressed in HCC patients and was mainly derived from tumor-associated macrophages. Furthermore, we found that high expression of IL-26 was associated with good prognosis due to its inhibition of HCC cell migration and invasion abilities. This function of IL-26 was driven by JAK-STAT3-dependent autophagy. These findings suggest that the levels of IL-26 may be a useful prognostic marker for HCC patients and may offer insights into the clinical application of IL-26 in the future.