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.

白细胞介素 26 (IL-26) 是一种最近发现的 IL-20 亚家族细胞因子，在调节宿主防御和炎症性疾病中起重要作用。然而，IL-26 在肝细胞癌 (HCC) 进展中的作用是否通过自噬发生仍不清楚。在这里，我们研究了受试者血液和组织中的 IL-26 水平、其可能的细胞来源及其与 HCC 患者预后的关系。我们还探讨了不同病理生理水平的 IL-26 影响患者预后的机制；由于啮齿动物缺乏 IL-26 基因表达，这些研究仅在体外进行。我们发现 IL-26 在 HCC 患者中高表达，主要来源于肿瘤相关巨噬细胞。此外，我们发现 IL-26 的高表达与良好的预后相关，因为它抑制了 HCC 细胞迁移和侵袭能力。IL-26 的这种功能是由 JAK-STAT3 依赖性自噬驱动的。这些发现表明，IL-26 的水平可能是 HCC 患者有用的预后标志物，并可能为未来 IL-26 的临床应用提供见解。