Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients

Abstract

To characterize IL-17-producing cells, a newly defined T helper cell subset with potent pro-inflammatory properties, in hepatocellular carcinoma (HCC) and to determine their prognostic values. One hundred and seventy-eight HCC patients were enrolled randomly. Distribution and phenotypic features of IL-17-producing cells were determined by flow cytometry and/or immunohistochemistry. Compared with corresponding non-tumor regions, the levels of Th17 cells were significantly increased in tumors of HCC patients (P<0.001). Most intratumoral Th17 cells exhibited an effector memory phenotype with increased expression of CCR4 and CCR6. Intratumoral IL-17-producing cell density was associated with overall survival (OS, P=0.001) and disease-free survival (DFS, P=0.001) in HCC patients. Multivariate Cox analysis revealed that intratumoral IL-17-producing cell density was an independent prognostic factor for OS (HR=2.351, P=0.009) and DFS (HR=2.256, P=0.002). Moreover, the levels of intratumoral Th17 cells were positively correlated with microvessel density in tumors (r=0.616, P=0.001). Accumulation of intratumoral IL-17-producing cells may promote tumor progression through fostering angiogenesis, and intratumoral IL-17-producing cell could serve as a potential prognostic marker and a novel therapeutic target for HCC.