Foxp3 expression in CD4+CD25+Foxp3+ regulatory T cells promotes development of colorectal cancer by inhibiting tumor immunity

J Huazhong Univ Sci Technolog Med Sci. 2016 Oct;36(5):677-682. doi: 10.1007/s11596-016-1644-1. Epub 2016 Oct 18.

Abstract

The mechanism underlying CD4+CD25+Foxp3+ regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4+CD25+Foxp3+Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0.01). Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at mRNA level (r=0.526, P=0.036), and was positively correlated with IL-10 at protein level (r=0.314, P=0.030). The Foxp3 expressed in CD4+CD25+Foxp3+Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC (P<0.05 for all). The IL-10 expression was correlated with the histological grade and TNM stage (both P<0.05). The Stat3 expression was correlated with the lymph node metastasis and TNM stage (both P<0.05). It was concluded that CD4+CD25+Foxp3+Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4+CD25+Foxp3+Tregs correlates with CRC progression.

Keywords: CD4+CD25+Foxp3+ regulatory T cells; Foxp3; IL-10; Stat3; colorectal cancer; tumor immunity.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / immunology
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Immunity / genetics
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • STAT3 Transcription Factor / biosynthesis*
  • STAT3 Transcription Factor / immunology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Interleukin-10