Intrahepatic interleukin-17+ T cells and FoxP3+ regulatory T cells cooperate to promote development and affect the prognosis of hepatocellular carcinoma

Abstract

Background and aim: Recent studies have shown that imbalance between tumor-infiltrating interleukin (IL)-17(+) T cells and regulatory T cells (Tregs) is an important regulator of progression in various cancers, but little is known regarding this imbalance in hepatocellular carcinoma (HCC). This study explored the role of imbalance between IL-17(+) T cells and Tregs in the immunopathogenesis of HCC in patients with chronic hepatitis B (CHB) infection.

Methods: Fifty-six of patient-matched tumors and peritumoral surgical specimens from 56 patient with HCC and 136 liver biopsies specimens from 46 patients with CHB, 37 with atypical hyperplasia (AH), and 53 with HCC were enrolled. The expressions of IL-17, FoxP3, CD4, and CD8 in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes.

Results: The density of liver infiltrated FoxP3(+) Tregs was increased in a stepwise manner from CHB to AH then HCC, while there was a decreasing trend for the density of IL-17(+) T cells and CD8(+) T cells. In surgical specimens of less differentiated HCC, the quantity of tumor-infiltrating FoxP3(+) Tregs was significantly lower and IL-17(+) T cells and CD8(+) T cells were significantly higher. Additionally, peritumoral IL-17(+) T cells were increased in poorly differentiated HCC. High intratumoral FoxP3(+) Tregs with high intratumoral IL-17(+) T cells showed a significantly lower overall survival (OS) and disease-free survival (DFS) compared with other groups (OS, P = 0.033; DFS, P = 0.004). High intratumoral FoxP3(+) Tregs with high peritumoral IL-17(+) T cells showed a significantly lower survival rate compared with other groups (OS, P < 0.001 and DFS, P < 0.001).

Conclusion: Our findings suggest that intrahepatic IL-17(+) T cells and FoxP3(+) Tregs may cooperate to promote the progression of HCC.

Keywords: IL-17+ T cells; atypical hyperplasia; chronic hepatitis B; hepatocellular carcinoma; regulatory T cells.