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Open Access 01-02-2008 | Original Article

Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

Authors: Akash M. Mehta, Ekaterina S. Jordanova, Gemma G. Kenter, Soldano Ferrone, Gert- Jan Fleuren

Published in: Cancer Immunology, Immunotherapy | Issue 2/2008

Abstract

HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β₂-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P < 0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P = 0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P < 0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P < 0.05 and HR 2.84; P < 0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality.

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Title: Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma
Authors: Akash M. Mehta
Ekaterina S. Jordanova
Gemma G. Kenter
Soldano Ferrone
Gert- Jan Fleuren
Publication date: 01-02-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 2/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0362-8

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