Epigenetic Enhancement of Antigen Processing and Presentation Promotes Immune Recognition of Tumors

A. F. Setiadi, K. Omilusik, M. D. David, R. P. Seipp, J. Hartikainen, R. Gopaul, K. B. Choi, W. A. Jefferies
2008 Cancer Research  
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 G 1 and G 2 -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
more » ... tigen 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] Note:
doi:10.1158/0008-5472.can-07-5270 pmid:19047136 fatcat:5zslxvg3mvebziomd2bxmwwbwe