Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma

  • Authors:
    • U. Ritz
    • F. Momburg
    • H. Pilch
    • C. Huber
    • M. J. Maeurer
    • B. Seliger
  • View Affiliations

  • Published online on: December 1, 2001     https://doi.org/10.3892/ijo.19.6.1211
  • Pages: 1211-1220
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Abstract

In cervical carcinomas abnormalities in the MHC class I surface expression are a frequent event, which are often associated with the deficient expression of the peptide transporter subunit TAP1 thereby resulting in impaired T cell response. In order to understand the role of other components of the MHC class I antigen processing machinery (APM) in the immune escape, 16 surgically removed primary cervical carcinoma lesions were analyzed for their mRNA expression of the heterodimeric peptide transporter TAP, the constitutive and interferon (IFN)-γ inducible proteasome subunits and their activators PA28α/β, various chaperones as well as MHC class I antigens. High expression levels of all APM components were detected in normal cervical tissue, whereas 15/16 of cervical carcinoma lesions exhibited an impaired expression of at least one APM component, including the proteasome subunits, their activators PA28α/β, the peptide transporter subunits TAP1 and TAP2, different chaperones, HLA class I heavy chains and β2-microglobulin (β2-m). In particular, calnexin expression was strongly downregulated in 69% of cervical cancer lesions analyzed. Such abnormalities were neither associated with a specific human papilloma virus (HPV) or HLA class I phenotype nor with tumor grading and staging. Analysis of five cervical carcinoma cell lines demonstrated a reduced MHC class I surface expression due to deficient expression and function of TAP, LMP subunits or specific HLA-alleles which could be mostly corrected by IFN-γ treatment. The high frequency of abnormalities of APM component expression together with their potential negative influence on T cell-mediated immune recognition emphasize the need to evaluate the antigen processing pathway in cervical carcinoma patients, particularly in those selected for T-cell-based immunotherapies.

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December 2001
Volume 19 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ritz U, Momburg F, Pilch H, Huber C, Maeurer MJ and Seliger B: Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol 19: 1211-1220, 2001
APA
Ritz, U., Momburg, F., Pilch, H., Huber, C., Maeurer, M.J., & Seliger, B. (2001). Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. International Journal of Oncology, 19, 1211-1220. https://doi.org/10.3892/ijo.19.6.1211
MLA
Ritz, U., Momburg, F., Pilch, H., Huber, C., Maeurer, M. J., Seliger, B."Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma". International Journal of Oncology 19.6 (2001): 1211-1220.
Chicago
Ritz, U., Momburg, F., Pilch, H., Huber, C., Maeurer, M. J., Seliger, B."Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma". International Journal of Oncology 19, no. 6 (2001): 1211-1220. https://doi.org/10.3892/ijo.19.6.1211