Effects of transarterial chemoembolization on regulatory T cell and its subpopulations in patients with hepatocellular carcinoma

Hepatol Int. 2020 Mar;14(2):249-258. doi: 10.1007/s12072-020-10014-4. Epub 2020 Feb 18.

Abstract

Background: Regulatory T cell (Treg) plays an essential role in regulating anti-tumor immunity. The aim of this study was to investigate the effect of transarterial chemoembolization (TACE) on Treg in hepatocellular carcinoma (HCC) patients.

Method: The frequency of peripheral blood Tregs in 27 HCC patients who underwent TACE were measured at baseline and 1 month after TACE. The frequency of peripheral blood Tregs at baseline were compared with those in 23 healthy controls. Tregs were further classified into three subpopulations [Treg (I), Treg (II), Treg (III)] based on expression levels or markers and their function. The patients were divided into two groups according to tumor response after TACE; complete response group and incomplete response group. The correlations between the frequency of Treg and clinical factors were analyzed.

Results: The frequency of Treg in HCC patients (7.52%) was significantly higher than in healthy controls (4.99%) at baseline. Regarding Treg subpopulations, the frequency of Treg (II) was significantly higher in HCC patients (2.51%) than in healthy controls (0.60%). In comparison of Treg numbers at baseline and post-TACE by tumor response, the change of Treg (III) in complete response group from baseline to post-TACE was significantly decreased (63.8 → 53.2/mm3). Patients with a high post-TACE Treg (III) (3.8 months) exhibited a significantly shorter median time to progression than those with a low post-TACE Treg (III) (11.6 months). In multivariate analyses, hypoalbuminemia (hazard ratio 3.324; 95% CI 1.098-10.063, p = 0.034) and high post-TACE Treg (III) (hazard ratio 3.080; 95% CI 1.091-8.696, p = 0.034) were significant factors for associating with progression.

Conclusions: The frequency of Tregs in HCC patients was significantly higher than in healthy controls. In addition, patients with a high post-TACE Treg (III) exhibited a significantly lower progression-free survival rate than those with a low post-TACE Treg (III).

Keywords: Hepatocellular carcinoma; Regulatory T cell; Transarterial chemoembolization; Treg.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Case-Control Studies
  • Chemoembolization, Therapeutic
  • Female
  • Humans
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / cytology*