Correlation between infiltration of FOXP3+ regulatory T cells and expression of B7-H1 in the tumor tissues of gastric cancer

Exp Mol Pathol. 2014 Jun;96(3):284-91. doi: 10.1016/j.yexmp.2014.03.005. Epub 2014 Mar 20.

Abstract

Background: Substantial evidence suggests that the expansion of regulatory T cells (T(regs)) plays a pivotal role in immunological evasion of tumors. Recent studies have demonstrated that a majority of tumor cells overexpress B7-H1, and this overexpression is associated with poor disease prognosis. Although an increase of T(regs) and B7-H1 has been revealed in several malignancies, their correlation in gastric cancer has not been studied.

Methods: Tumor sections from 111 gastric cancer patients were stained for FOXP3 and B7-H1 by immunohistochemistry. The expression levels of these two molecules were statistically associated with various factors involved in disease progression and prognosis. The correlation between their expression levels was analyzed.

Results: The infiltration of FOXP3(+) T(regs) and expression of B7-H1 were observed in gastric cancer tissues, and there was a highly significant correlation between these two molecules (P < 0.01). The expression of FOXP3(+) T(regs) and B7-H1 was associated with lymph node metastasis and the clinicopathological stage and prognosis of gastric cancer patients. The expression levels of these two determinants in patients with lymph node metastasis and an advanced clinicopathological stage were distinctly higher (P < 0.05). The patients with enhanced expression of FOXP3(+) T(regs) and B7-H1 exhibited a lower overall survival rate and a worse prognosis (P < 0.05).

Conclusions: Increased expression of FOXP3(+) T(regs) and B7-H1 was observed in gastric cancer tissues; the two molecules were closely correlated with each other, suggesting that they might be used as new biomarkers to predict the disease progression and prognosis. Combinatorial immunotherapeutic approaches based on depleting the T(regs) and blocking B7-H1 might improve therapeutic efficacy in gastric cancer.

Keywords: B7-H1; Clinicopathology; Correlation; FOXP3(+) T(regs); Gastric cancer; Prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • Up-Regulation
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors