title: MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and -gamma.
abstract: BACKGROUND
  Expression of Major Histocompatibility Complex (MHC) class I and II antigens are critical for the cellular immune response. Loss of MHC expression represents one mechanism by which cancer cells escape immune recognition.
  
  
  OBJECTIVE
  To define MHC class I and II expression by prostate cancer (PCa) in vivo and in vitro and the ability to modulate MHC expression in vitro with IFN-alpha and -gamma.
  
  
  METHODS
  Frozen tissue sections of 25 benign prostatic hyperplasia (BPH) and 18 PCa specimens were studied by immunohistochemistry. PCa cell lines LNCaP, PC-3, and DU-145 were studied by FACS, ELISA, and cytospin. Class I was detected by monoclonal antibody (mAb) W6/32, and class II by mAb 13.17. The effects of IFN-alpha and -gamma were assessed by testing the three cell lines in the presence or absence of varying concentrations of the cytokine for varying incubation times.
  
  
  RESULTS
  Class I was strongly expressed by 24/25 BPH specimens; 4/18 (22%) PCa were homogeneously class I-positive, while 5/18 (28%) were heterogeneously positive and 9/18 (50%) were class I-negative. PC-3 and DU-145 expressed normal levels of class I, while LNCaP expressed only low levels. All line except LNCaP demonstrated significant up-regulation of class I with either IFN-alpha or -gamma. Class II expression was not seen in BPH epithelium nor in 17/18 PCa. Class II could be only weakly induced in the three PCa lines.
  
  
  CONCLUSIONS
  These findings confirm prior studies demonstrating that class I expression is commonly lost or diminished in PCa. In addition, class II up-regulation by IFN-gamma appears very limited in relation to other normal or neoplastic epithelium.
  
  
  CONCLUSIONS
  The present findings, taken together with previous studies, are most consistent with the expression of neoantigens by PCa, which are recognized and appropriately eliminated by the cellular immune system. This selective pressure favors outgrowth of cells which down-regulate or lose class I and/or class II expression. Understanding PCa immunobiology will help in the development of effective immunotherapy for this disease.
authors.affiliation: Department of Urology, New York Hospital-Cornell Medical Center, New York, NY 10021, USA. nhbander@mail.med.cornell.edu
authors.forename: N H
authors.initials: NH
authors.lastname: Bander
authors.forename: D
authors.initials: D
authors.lastname: Yao
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: Y T
authors.initials: YT
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Steiner
authors.forename: W
authors.initials: W
authors.lastname: Zuccaro
authors.forename: P
authors.initials: P
authors.lastname: Moy
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D011470:Prostatic Hyperplasia / Q000276:immunology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; D007371:Interferon-gamma