Increased circulating Th17 cells after transarterial chemoembolization correlate with improved survival in stage III hepatocellular carcinoma: a prospective study

PLoS One. 2013;8(4):e60444. doi: 10.1371/journal.pone.0060444. Epub 2013 Apr 2.


Transarterial chemoembolization (TACE) has therapeutic effects in patients with unresectable hepatocellular carcinoma (HCC), but its impact on the cellular immune response during disease progression is largely unknown. Here we conducted a prospective study to evaluate the effect of TACE on immune status and to identify prognostic immune markers governing treatment success. In this study, 51 stage III HCC patients, 28 stage I HCC patients (TNM classification) and 20 healthy donors were enrolled. Flow cytometry and cytometric bead array were used to evaluate the circulating immune cell subsets, including CD4(+) T cells (Th1, Th17 and Treg cells), CD8(+) T cells, NK cells, and NKT cells, and plasma cytokines before TACE and 30 days after TACE. Interestingly, among those immune parameters, the frequency of circulating Th17 cells was higher in stage III HCC patients than in stage I HCC patients (P = 0.015) and healthy donors (P<0.001). Moreover, an increased frequency of circulating Th17 cells was observed 30 days after TACE (Th17 D30 ) compared with the baseline level (P = 0.036). Kaplan-Meier analysis demonstrated that Th17 D30 was positively associated with overall survival (OS; P = 0.007) and time to progression (TTP; P = 0.009). Multivariate Cox analysis revealed that Th17 D30 was an independent prognostic factor for OS (HR = 0.317, P = 0.032) and TTP (HR = 0.304, P = 0.010). These results provide a potential prognostic marker for stage III HCC patients undergoing TACE and may be useful for identifying patients who can benefit from adjuvant immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / therapy*
  • Chemoembolization, Therapeutic*
  • Female
  • Humans
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / therapy*
  • Male
  • Prospective Studies
  • Th17 Cells / immunology*
  • Treatment Outcome

Grant support

This work was supported by grants from the Ministry of Health of China (2012ZX10002-011), the National Natural Science Foundation of China (30901355, 91029737 and 30872372), the Fundamental Research Funds for the Central Universities (11lgpy57) and the Natural Science Foundation of Guangdong Province (S2011010001393). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.