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MHC class I and II expression in prostate carcinoma and modulation by interferon‐alpha and ‐gamma
Author(s) -
Bander Neil H.,
Yao Daniel,
Liu He,
Chen YaoTseng,
Steiner Melissa,
Zuccaro Wendy,
Moy Peggy
Publication year - 1997
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19971201)33:4<233::aid-pros2>3.0.co;2-i
Subject(s) - prostate carcinoma , prostate , immune modulation , interferon gamma , carcinoma , mhc class i , major histocompatibility complex , medicine , alpha (finance) , oncology , immunology , cancer research , immune system , cancer , surgery , construct validity , patient satisfaction
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. PURPOSE 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‐α and ‐γ. 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 DU145 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‐α and ‐γ 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 lines except LNCaP demonstrated significant up‐regulation of class I with either IFN‐α or ‐γ. 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‐γ appears very limited in relation to other normal or neoplastic epithelium. IMPLICATIONS 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. Prostate 33:233–239, 1997. © 1997 Wiley‐Liss, Inc.