title: Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer.
abstract: Defects in HLA class I antigen processing machinery (APM) component expression often have a negative impact on the clinical course of tumors and on the response to T cell-based immunotherapy. Since only scant information is available about the frequency and clinical significance of HLA class I APM component abnormalities in prostate cancer, the APM component expression pattern was analyzed in 59 primary prostate carcinoma, adjacent normal tissues, as well as in prostate carcinoma cell lines. The IFN-gamma 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 beta(2)-microglobulin are expressed on the cell surface. Most of the APM components were downregulated in a substantial number of prostate cancers. With the exception of HLA class I HC, TAP2 and ERp57 not detectable in about 0.5% of tumor lesions, all other APM components were not detected in at least 21% of lesions analyzed. These APM component defects were associated with a higher Gleason grade of tumors and an early disease recurrence. Prostate carcinoma cell lines also exhibit a heterogeneous, but reduced constitutive APM component expression pattern associated with lack or reduced HLA class I surface antigens, which could be upregulated by IFN-gamma. Our 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.
authors.affiliation: Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112 Halle, Germany. Barbara.Seliger@medizin.uni-halle.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Diana
authors.initials: D
authors.lastname: Handke
authors.forename: Anja
authors.initials: A
authors.lastname: Mueller
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000368:Aged; D017951:Antigen Presentation; D000998:Antiviral Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology*; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000998:Antiviral Agents; D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D007371:Interferon-gamma