Sequential 5-Aza-2′-deoxycytidine-Depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1

T. S. Weiser, Z. Sheng Guo, G. A. Ohnmacht, M. L. Parkhurst, P. Tong-On, F. M. Marincola, M. R. Fischette, X. Yu, G. A. Chen, J. A. Hong, J. H. Stewart, Dao Nguyen, S. A. Rosenberg, D. S. Schrump

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Global alterations in chromatin structure profoundly influence gene expression in thoracic neoplasms, silencing tumor suppressors while facilitating the expression of various cancer testis antigens such as NY-ESO-1. Although recent studies have shown that histone deacetylase inhibitors can potentiate tumor suppressor gene induction mediated by demethylating agents in cancer cells, the ability of these agents to augment cancer testis antigen expression have not been fully defined. The authors designed the current study to determine whether the histone deacetylase inhibitor, depsipeptide FR901228 (DP), could enhance NY-ESO-1 induction mediated by the DNA demethylating agent 5-Aza-2′-deoxycytidine (DAC) in cell lines established primarily from thoracic cancers. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed that, under exposure conditions potentially achievable in clinical settings, DAC dramatically induced NY-ESO-1 expression in cultured cancer lines. DP alone mediated negligible target gene induction but significantly augmented DAC-mediated induction of NY-ESO-1. After DAC or sequential DAC-DP treatment. HLA-A*0201 cancer cells were recognized by an HLA-A*0201 CTL specific for NY-ESO-1. Although sequential DAC/DP exposure did not uniformly enhance immune recognition of target cells compared with DAC alone, this treatment mediated profound induction of apoptosis in cancer cells but not normal human bronchial epithelia. The apoptotic effects of DAC, DP, or sequential DAC-DP did not correlate in an obvious manner with histology, or the magnitude of NY-ESO-1 induction in cancer cells. Although the mechanisms have not been fully defined, sequential DAC-DP treatment may be a novel strategy to augment antitumor immunity in cancer patients.

Original languageEnglish
Pages (from-to)151-161
Number of pages11
JournalJournal of Immunotherapy
Volume24
Issue number2
DOIs
StatePublished - Mar 12 2001
Externally publishedYes

Fingerprint

decitabine
Depsipeptides
Apoptosis
T-Lymphocytes
Neoplasms
Histone Deacetylase Inhibitors
Testicular Neoplasms
Thoracic Neoplasms
Antigens
romidepsin
Tumor Suppressor Genes
Reverse Transcriptase Polymerase Chain Reaction
Chromatin

Keywords

  • 5-Aza-2′-deoxycytidine
  • Apoptosis
  • Depsipeptide FR901228
  • Esophageal cancer
  • Gene induction
  • Lung cancer
  • Malignant pleural mesothelioma
  • Melanoma
  • NY-ESO-1
  • Tumor immunology

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Sequential 5-Aza-2′-deoxycytidine-Depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1. / Weiser, T. S.; Sheng Guo, Z.; Ohnmacht, G. A.; Parkhurst, M. L.; Tong-On, P.; Marincola, F. M.; Fischette, M. R.; Yu, X.; Chen, G. A.; Hong, J. A.; Stewart, J. H.; Nguyen, Dao; Rosenberg, S. A.; Schrump, D. S.

In: Journal of Immunotherapy, Vol. 24, No. 2, 12.03.2001, p. 151-161.

Research output: Contribution to journalArticle

Weiser, TS, Sheng Guo, Z, Ohnmacht, GA, Parkhurst, ML, Tong-On, P, Marincola, FM, Fischette, MR, Yu, X, Chen, GA, Hong, JA, Stewart, JH, Nguyen, D, Rosenberg, SA & Schrump, DS 2001, 'Sequential 5-Aza-2′-deoxycytidine-Depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1', Journal of Immunotherapy, vol. 24, no. 2, pp. 151-161. https://doi.org/10.1097/00002371-200103000-00010
Weiser, T. S. ; Sheng Guo, Z. ; Ohnmacht, G. A. ; Parkhurst, M. L. ; Tong-On, P. ; Marincola, F. M. ; Fischette, M. R. ; Yu, X. ; Chen, G. A. ; Hong, J. A. ; Stewart, J. H. ; Nguyen, Dao ; Rosenberg, S. A. ; Schrump, D. S. / Sequential 5-Aza-2′-deoxycytidine-Depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1. In: Journal of Immunotherapy. 2001 ; Vol. 24, No. 2. pp. 151-161.
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