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Semi-quantitative Detection of RNA-dependent RNA Polymerase Activity of Human Telomerase Reverse Transcriptase Protein
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Presentation of telomerase reverse transcriptase, a self-tumor antigen, is down-regulated by histone deacetylase

Ilenia Pellicciotta1, Xochitl Cortez-Gonzalez, Roman Sasik

  • 1Department of Medicine, Moores Cancer Center, The Laboratory of Immunology, University of California, La Jolla, California92093-0815, USA.

Cancer Research
|October 3, 2008
PubMed

Insights

Histone deacetylase (HDAC) inhibition decreases tumor antigen presentation and cytotoxic T lymphocyte (CTL) killing of cancer cells. This epigenetic change may help tumors evade immune surveillance.

Area of Science:

  • Immunology
  • Epigenetics
  • Cancer Biology

Background:

  • Histone deacetylases (HDAC) regulate gene expression by altering chromatin structure.
  • HDAC inhibition can impact cell proliferation, cancer, and immune T cell differentiation.
  • The effect of HDAC inhibition on anti-tumor T cell-tumor cell interactions remains unclear.

Purpose of the Study:

  • To investigate the impact of HDAC inhibition on the presentation of tumor antigens in human cancer cells.
  • To determine how HDAC inhibition affects the interaction between cytotoxic T lymphocytes (CTLs) and tumor cells.

Main Methods:

  • Treatment of human tumor cells with trichostatin A (an HDAC inhibitor).
  • Analysis of telomerase reverse transcriptase (a self-tumor antigen) presentation.
  • Gene array analysis to identify changes in gene expression.
  • Assessment of CTL-mediated tumor cell killing.

Main Results:

  • HDAC inhibition led to decreased presentation of the self-tumor antigen, telomerase reverse transcriptase.
  • Trichostatin A treatment resulted in diminished killing of tumor cells by CTLs.
  • Gene array analysis revealed reduced expression of genes involved in proteasome function and MHC class I antigen presentation (including tapasin).

Conclusions:

  • Epigenetic modifications induced by HDAC inhibition can reduce self-tumor antigen presentation in cancer cells.
  • This reduced antigen presentation impairs recognition and killing of tumor cells by CTLs.
  • The findings suggest a mechanism by which tumors may escape immune surveillance through HDAC inhibition-mediated epigenetic changes.

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