Tumor-infiltrating FoxP3+ Tregs and CD8+ T cells affect the prognosis of hepatocellular carcinoma patients

Digestion. 2012;86(4):329-37. doi: 10.1159/000342801. Epub 2012 Nov 28.

Abstract

Purpose: Tumor-infiltrating lymphocytes are considered to represent a host immune response against tumor. This study was carried out to analyze the effect of both FoxP3+ regulatory T cells (Tregs) and CD8+ T lymphocytes in prognostic value of hepatocellular carcinoma (HCC) patients.

Methods: Expressions of FoxP3, CD4, CD8 and CD34 in patient-matched tumors and peritumoral tissues were assessed by immunohistochemistry for 54 HCC patients. The prognostic effect of groups with high and low numbers was evaluated by the Kaplan-Meier and Cox model analysis using median values as a cutoff.

Results: Compared with the corresponding peritumoral tissue, the density of intratumoral Tregs was significantly higher, while the density of intratumoral CD8+ T cells was lower (p < 0.001 and p = 0.013, respectively). In addition, tumor-infiltrating Tregs were positively correlated with microvessel density in tumors (r = 0.334, p = 0.020). The high intratumoral Tregs density group showed a significantly lower survival rate (overall survival, p = 0.018; disease-free survival, p = 0.029). Multivariate Cox analysis revealed that intratumoral Tregs density was an independent prognostic factor for HCC.

Conclusions: Tumor-infiltrating Tregs may promote HCC progression by fostering angiogenesis and decreasing CD8+ T cells. High tumor-infiltrating Tregs are thought to be an unfavorable prognostic indicator for HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34
  • CD4 Antigens
  • CD8 Antigens
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / immunology*
  • Disease-Free Survival
  • Female
  • Forkhead Transcription Factors / immunology*
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Liver / metabolism
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / immunology*
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Microvessels / pathology
  • Middle Aged
  • Proportional Hazards Models
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Microenvironment / immunology

Substances

  • Antigens, CD34
  • CD4 Antigens
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors