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Titolo:
Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma
Autore:
Ritz, U; Momburg, F; Pilch, H; Huber, C; Maeurer, MJ; Seliger, B;
Indirizzi:
Univ Mainz, Dept Internal Med 3, D-55101 Mainz, Germany Univ Mainz MainzGermany D-55101 Internal Med 3, D-55101 Mainz, Germany Univ Mainz, Dept Gynecol, D-55101 Mainz, Germany Univ Mainz Mainz Germany D-55101 z, Dept Gynecol, D-55101 Mainz, Germany Univ Mainz, Dept Med Microbiol, D-55101 Mainz, Germany Univ Mainz Mainz Germany D-55101 t Med Microbiol, D-55101 Mainz, Germany German Canc Res Ctr, D-69120 Heidelberg, Germany German Canc Res Ctr Heidelberg Germany D-69120 69120 Heidelberg, Germany
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 6, volume: 19, anno: 2001,
pagine: 1211 - 1220
SICI:
1019-6439(200112)19:6<1211:DEOCOT>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAJOR-HISTOCOMPATIBILITY-COMPLEX; HLA-CLASS-I; DOWN-REGULATION; PEPTIDE TRANSPORTERS; ENDOPLASMIC-RETICULUM; TAP-1 EXPRESSION; UP-REGULATION; CELL-LINES; IFN-GAMMA; MOLECULES;
Keywords:
cervical cancer; HLA; antigen processing; human papilloma virus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Seliger, B Univ Mainz, Dept Internal Med 1, Langenbeckstr 1, D-55101 Mainz, Germany Univ Mainz Langenbeckstr 1 Mainz Germany D-55101 ainz, Germany
Citazione:
U. Ritz et al., "Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma", INT J ONCOL, 19(6), 2001, pp. 1211-1220

Abstract

In cervical carcinomas abnormalities in the MHC class I surface expressionare a frequent event, which are often associated with the deficient expression of the peptide transporter subunit TAP I thereby resulting in impairedT 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)-gamma inducible proteasome subunits and their activators PA28 alpha/beta, 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 PA28 alpha/beta, the peptide transporter subunits TAP1 and TAP2, different chaperones, HLA class I heavy chains and B-2-microglobulin (beta (2)-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 specificHLA-alleles which could be mostly corrected by IFN-gamma 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 15:29:01