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Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer
Cancer Immunology, Immunotherapy, 10/26/09

Seliger B et al. – Results suggest that HLA class I APM component abnormalities are mainly due to regulatory mechanisms, play a role in the clinical course of prostate cancer and on the outcome of T cell-based immunotherapies

Methods

APM component expression pattern analyzed in 59 primary prostate carcinoma, adjacent normal tissues, as well as in prostate carcinoma cell lines

Results

IFN-? inducible proteasome subunits LMP2 and LMP7, TAP1, TAP2, calnexin, calreticulin, ERp57, and tapasin are strongly expressed in the cytoplasm of normal prostate cells, whereas HLA class I heavy chain (HC) and ?2-microglobulin are expressed on the cell surface
Most of APM components downregulated in substantial number of prostate cancers
With exception of HLA class I HC, TAP2 and ERp57 not detectable in about 0.5% of tumor lesions, all other APM components not detected in at least 21% of lesions analyzed
APM component defects associated with higher Gleason grade of tumors and early disease recurrence
Prostate carcinoma cell lines also exhibit heterogeneous, but reduced constitutive APM component expression pattern associated with lack or reduced HLA class I surface antigens, which could be upregulated by IFN-&upsilon