Interleukin 22 is related to development and poor prognosis of hepatocellular carcinoma

Background and aims: Immune response against hepatitis B virus (HBV) infection is an important risk factor for the development of hepatocellular carcinoma (HCC). Studies have reported that interleukin 22 (IL-22) exhibits both protective and pathological properties in liver diseases. Our aim was to explore the importance of IL-22 in the development of HCC, and to characterize the relationship between IL-22 levels and the prognosis of HCC. Methods: Totally, 136 liver biopsy specimens from 46 patients with chronic hepatitis B (CHB), 37 with atypical hyperplasia (AH), 53 with HCC, patient-matched tumors and peritumoral surgical specimens from 56 HCC patients included in the study. The expression of IL-22 and CD8 was evaluated by immunochemistry. Corresponding serum samples were collected from 30 CHB, 30 AH, and 30 HCC patients. IL-22 expression was determined by an enzyme linked immunosorbent assay. Results: Liver-infiltrating IL-22(+) cells increased in a stepwise manner from CHB to AH and HCC (CHB vs. AH, P = 0.002; AH vs. HCC, P = 0.010), whereas a decreasing trend was observed for CD8(+) T cells (CHB vs. AH, P = 0.031; AH vs. HCC, P = 0.652). Serum IL-22 levels also increased from CHB to AH and HCC (CHB vs. AH, P = 0.024; AH vs. HCC, P = 0.026). Tumor-infiltrating IL-22(+) cells and serum IL-22 were associated with histologic grade (P = 0.024 and P = 0.033). Additionally, CD8(+) T cells correlated with tumor size (P = 0.032). Furthermore, the high intratumoral IL-22(+) cell group and high serum IL-22 group showed lower overall survival (OS; P = 0.001, P = 0.017) and disease-free survival (DFS; P = 0.005, P < 0.001). Multivariate analysis revealed that intratumoral IL-22(+) cells and serum IL-22 levels were independent prognostic factors for both OS and DFS. Conclusions: These findings indicate that IL-22 promotes the progression of HCC in CHB patients. High tumor-infiltrating IL-22(+) cells and serum IL-22 levels are thought to be unfavorable prognostic indicators for HCC. (C) 2020 Published by Elsevier Masson SAS.