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An epigenetically altered tumor cell vaccine. | LitMetric

An epigenetically altered tumor cell vaccine.

Cancer Immunol Immunother

Laboratory of Molecular Medicine, Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Published: August 2004

AI Article Synopsis

  • The study investigates how gene silencing, a process that can reduce immune responses, might be reversed to create effective tumor vaccines.
  • Researchers used a histone deacetylase inhibitor, trichostatin A (TSA), to modify the expression of key immune genes in tumor cells, resulting in slowed tumor growth in mouse models.
  • Findings suggest that reversing immune gene repression can enhance tumor immunity, potentially leading to new strategies in cancer treatment.

Article Abstract

Functional inactivation of genes critical to immunity may occur by mutation and/or by repression, the latter being potentially reversible with agents that modify chromatin. This study was constructed to determine whether reversal of gene silencing, by altering the acetylation status of chromatin, might lead to an effective tumor vaccine. We show that the expression of selected genes important to tumor immunity, including MHC class II, CD40, and B7-1/2 are altered by treating tumor cells in vitro with a histone deacetylase inhibitor, trichostatin A (TSA). Tumor cells treated in vitro with TSA showed delayed onset and rate of tumor growth in 70% of the J558 plasmacytoma and 100% of the B16 melanoma injected animals. Long-term tumor specific immunity was elicited to rechallenge with wild-type cells in approximately 30% in both tumor models. Splenic T cells from immune mice lysed untreated tumor cells, and SCID mice did not manifest immunity, suggesting that T cells may be involved in immunity. We hypothesize that repression of immune genes is involved in the evasion of immunity by tumors and suggest that epigenetically altered cancer cells should be further explored as a strategy for the induction of tumor immunity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032794PMC
http://dx.doi.org/10.1007/s00262-004-0513-0DOI Listing

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