The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China; Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin 300170, China.
Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin 300170, China.
Clin Res Hepatol Gastroenterol. 2020 Nov;44(6):855-864. doi: 10.1016/j.clinre.2020.01.009. Epub 2020 Mar 20.
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.
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.
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.
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.
针对乙型肝炎病毒 (HBV) 感染的免疫反应是肝细胞癌 (HCC) 发展的一个重要危险因素。研究报告称，白细胞介素 22 (IL-22) 在肝脏疾病中具有保护和病理作用。我们的目的是探讨 IL-22 在 HCC 发展中的重要性，并描述 IL-22 水平与 HCC 预后之间的关系。
共纳入 46 例慢性乙型肝炎 (CHB)、37 例不典型增生 (AH)、53 例 HCC 患者的 136 份肝活检标本、56 例 HCC 患者的配对肿瘤和肿瘤旁手术标本。通过免疫化学法评估 IL-22 和 CD8 的表达。收集了 30 例 CHB、30 例 AH 和 30 例 HCC 患者的相应血清样本。通过酶联免疫吸附试验测定 IL-22 表达。
肝内浸润的 IL-22 细胞从 CHB 到 AH 和 HCC 呈逐步增加趋势(CHB 与 AH 比较，P=0.002；AH 与 HCC 比较，P=0.010)，而 CD8 T 细胞呈下降趋势(CHB 与 AH 比较，P=0.031；AH 与 HCC 比较，P=0.652)。血清 IL-22 水平也从 CHB 到 AH 和 HCC 逐渐升高(CHB 与 AH 比较，P=0.024；AH 与 HCC 比较，P=0.026)。肿瘤内浸润的 IL-22 细胞和血清 IL-22 与组织学分级有关(P=0.024 和 P=0.033)。此外，CD8 T 细胞与肿瘤大小相关(P=0.032)。此外，高肿瘤内 IL-22 细胞组和高血清 IL-22 组的总生存期(OS；P=0.001，P=0.017)和无病生存期(DFS；P=0.005，P<0.001)较低。多变量分析显示，肿瘤内 IL-22 细胞和血清 IL-22 水平是 OS 和 DFS 的独立预后因素。
这些发现表明，IL-22 促进了 CHB 患者 HCC 的进展。高肿瘤内浸润的 IL-22 细胞和血清 IL-22 水平可能是 HCC 的不利预后指标。
