PT  - JOURNAL ARTICLE
AU  - Setiadi, A. Francesca
AU  - Omilusik, Kyla
AU  - David, Muriel D.
AU  - Seipp, Robyn P.
AU  - Hartikainen, Jennifer
AU  - Gopaul, Rayshad
AU  - Choi, Kyung Bok
AU  - Jefferies, Wilfred A.
TI  - Epigenetic Enhancement of Antigen Processing and Presentation Promotes Immune Recognition of Tumors
AID  - 10.1158/0008-5472.CAN-07-5270
DP  - 2008 Dec 01
TA  - Cancer Research
PG  - 9601--9607
VI  - 68
IP  - 23
4099  - http://cancerres.aacrjournals.org/content/68/23/9601.short
4100  - http://cancerres.aacrjournals.org/content/68/23/9601.full
SO  - Cancer Res2008 Dec 01; 68
AB  - Histone deacetylase inhibitors (HDACi) have been hailed as a powerful new class of anticancer drugs. The HDACi, trichostatin A (TSA), is thought to interfere with epigenetic control of cell cycle progression in G1 and G2-M phase, resulting in growth arrest, differentiation, or apoptosis. Here, we describe a novel mechanism of action of HDACis in promoting immune responses against tumors. We report that treatment of carcinoma cells with TSA increases the expression of many components of the antigen processing machinery, including TAP-1, TAP-2, LMP-2, and Tapasin. Consistent with this result, we found that treatment of metastatic carcinoma cells with TSA also results in an increase in MHC class I expression on the cell surface that functionally translates into an enhanced susceptibility to killing by antigen-specific CTLs. Finally, we observed that TSA treatment suppresses tumor growth and increases tap-1 promoter activity in TAP-deficient tumor cells in vivo. Intriguingly, this in vivo anti-tumoral effect of TSA is entirely mediated by an increase in immunogenicity of the tumor cells, as it does not occur in immunodeficient mice. These novel insights into the molecular mechanisms controlling tumor immune escape may help revise immunotherapeutic modalities for eradicating cancers. [Cancer Res 2008;68(23):9601–7] ©2008 American Association for Cancer Research.