Presentation of telomerase reverse transcriptase, a self-tumor antigen, is down-regulated by histone deacetylase inhibition

Ilenia Pellicciotta, Xochitl Cortez-Gonzalez, Roman Sasik, Yoram Reiter, Gary Hardiman, Pierre Langlade-Demoyen, Maurizio Zanetti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Histone deacetylases (HDAC) modify the architecture of chromatin, leading to decreased gene expression, an effect that is reversed by HDAC inhibition. The balance between deacetylation and acetylation is central to many biological events including the regulation of cell proliferation and cancer but also the differentiation of immune T cells. The effects of HDAC inhibition on the interaction between antitumor effector T cells and tumor cells are not known. Here, we studied presentation of a universal self-tumor antigen, telomerase reverse transcriptase, in human tumor cells during HDAC inhibition. We found that HDAC inhibition with trichostatin A was associated with a decreased presentation and diminished killing of tumor cells by CTLs. Using gene array analysis, we found that HDAC inhibition resulted in a decrease of genes coding for proteasome catalytic proteins and for tapasin, an endoplasmic reticulum resident protein involved in the MHC class I pathway of endogenous antigen presentation. Our findings indicate that epigenetic changes in tumor cells decrease self-tumor antigen presentation and contribute to reduced recognition and killing of tumor cells by cytotoxic T lymphocytes. This mechanism could contribute to tumor escape from immune surveillance.

Original languageEnglish
Pages (from-to)8085-8093
Number of pages9
JournalCancer Research
Volume68
Issue number19
DOIs
Publication statusPublished - 01 Oct 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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