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Updated: Dec 25, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Interleukin 22 is related to development and poor prognosis of hepatocellular carcinoma
Jingxiang Shi1, Yijun Wang2, Fengmei Wang3
1The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China; Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin 300170, China.
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.
