Th inducing POZ-Kruppel Factor (ThPOK) is a key regulator of the immune response since the early steps of colorectal carcinogenesis

PLoS One. 2013;8(1):e54488. doi: 10.1371/journal.pone.0054488. Epub 2013 Jan 17.

Abstract

We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aberrant Crypt Foci / genetics
  • Aberrant Crypt Foci / immunology
  • Adenoma / metabolism
  • Adenoma / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Cell Transformation, Neoplastic*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology*
  • Gene Expression Regulation
  • Humans
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Transcription Factors / genetics*
  • Transcription Factors / immunology*

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • ZBTB7B protein, human

Grants and funding

This work was supported by the Fondazione Umberto Veronesi (which supported the grant for Dott. Francesco Mariani). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.