Cancer Immunology, Immunotherapy

, Volume 59, Issue 4, pp 529–540

Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer

  • Barbara Seliger
  • Robert Stoehr
  • Diana Handke
  • Anja Mueller
  • Soldano Ferrone
  • Bernd Wullich
  • Andrea Tannapfel
  • Ferdinand Hofstaedter
  • Arndt Hartmann
Original Article

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-γ 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 β2-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-γ. 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.

Keywords

Antigen processing machinery HLA class I antigens Immune escape Prostate cancer 

Abbreviations

APM

Antigen processing machinery

AR

Androgen receptor

ATCC

American tissue culture collection

β2-m

β2-Microglobulin

CTL

Cytotoxic T lymphocyte

FCS

Fetal calf serum

HC

Heavy chain

IFN

Interferon

LMP

Low molecular weight protein

mAb

Monoclonal antibody

MHC

Major histocompatibility complex

PC

Prostate carcinoma

PSA

Prostate-specific antigen

RCC

Renal cell carcinoma

TA

Tumor antigen

TAP

Transporter associated with antigen processing

tpn

Tapasin

TMA

Tissue microarray

TNF

Tumor necrosis factor

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Barbara Seliger
    • 1
  • Robert Stoehr
    • 2
  • Diana Handke
    • 1
  • Anja Mueller
    • 1
  • Soldano Ferrone
    • 3
  • Bernd Wullich
    • 4
  • Andrea Tannapfel
    • 5
  • Ferdinand Hofstaedter
    • 6
  • Arndt Hartmann
    • 2
  1. 1.Institute of Medical ImmunologyMartin Luther University Halle-WittenbergHalleGermany
  2. 2.Institute of PathologyUniversity Hospital ErlangenErlangenGermany
  3. 3.Departments of Surgery, of Immunology and of PathologyUniversity of Pittsburgh Cancer InstitutePittsburghUSA
  4. 4.Department of UrologyUniversity HospitalErlangenGermany
  5. 5.Institute of PathologyRuhr-University of BochumBochumGermany
  6. 6.Institute of PathologyUniversity of RegensburgRegensburgGermany

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