Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Kitamura, H. et al.

Hiroshi Kitamura, Toshihiko Torigoe, Hiroko Asanuma, Ichiya Honma, Noriyuki Sato, Taiji Tsukamoto,

Down-regulation of HLA class I antigens in prostate cancer tissues and up-regulation by histone deacetylase inhibition.

PURPOSE: HLA class I down-regulation in cancer cells confers immunological escape from cytotoxic T lymphocytes. We assessed the frequency of down-regulation of HLA class I antigens in a large series of prostate cancer tissues and determined the mechanism of up-regulation by investigating prostate cancer cell lines. MATERIALS AND METHODS: Immunohistochemical staining for HLA class I was done in specimens of 419 prostate cancers. We also investigated clinicopathological parameters, and the relationships between HLA class I down-regulation and the parameters. Furthermore, we examined whether HLA down-regulation was caused by epigenetic changes in vitro. RESULTS: HLA class I was down-regulated in 311 prostate cancers (74.2%) and it significantly correlated with beta2-microglobulin down-regulation and a higher clinical stage. Flow cytometric analysis revealed a low level of HLA class I in LNCaP cells, which was up-regulated by the histone deacetylase inhibitor trichostatin A (Sigma). Trichostatin A up-regulated LNCaP beta2-microglobulin at the protein level. Furthermore, chromatin immunoprecipitation assay using an anti-acetylated histone H3 antibody provided direct evidence that trichostatin A up-regulated beta2-microglobulin by modulating the acetylation status of the promoter region in LNCaP cells. CONCLUSIONS: The current study shows that the prevalence of HLA class I down-regulation is high in prostate cancer but histone deacetylase inhibitors can up-regulate HLA class I in LNCaP cells by up-regulating beta2-microglobulin. We suggest that the combination of an immunotherapeutic approach and histone deacetylase inhibition would accentuate the effects of current immunotherapies for prostate cancer.[1]

References

Down-regulation of HLA class I antigens in prostate cancer tissues and up-regulation by histone deacetylase inhibition. Kitamura, H., Torigoe, T., Asanuma, H., Honma, I., Sato, N., Tsukamoto, T. J. Urol. (2007) [Pubmed]

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