Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression.

2.50
Hdl Handle:
http://hdl.handle.net/10541/99451
Title:
Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression.
Authors:
Keating, P J; Cromme, F V; Duggan-Keen, Margaret F; Snijders, P J; Walboomers, Jan M; Hunter, Robin D; Dyer, P A; Stern, Peter L
Abstract:
The development of cervical carcinoma is strongly associated with specific types of human papillomaviruses (HPVs). A role for cellular immunity in cervical disease is supported by the increased occurrence of HPV-associated lesions in immunosuppressed individuals. Upon viral infection or malignant transformation, ensuing alterations in gene expression result in the generation of novel sets of peptides which can form complexes with specific HLA class I heavy chains and beta 2-microglobulin. These are then expressed at the cell surface as potential targets for specific T cells. In this study of 100 carcinomas HLA-A and -B class I expression by the tumour cells was down-regulated at one or more alleles in at least 73% of cervical carcinomas. Interference with the transporter associated with antigen presentation (TAP), which translocates cytosolic peptides from endogenously synthesised proteins (e.g. viral) into the lumen of the endoplasmic reticulum was found in 38% of the HLA class I down-regulated tumours. Loss of expression for common HLA class I alleles ranged from 36% to 71%, and such changes might be expected to influence specific immunogenic peptide presentation and consequent immune recognition. These results underline the importance of single as well as multiple allelic loss in cervical neoplasia and have important implications for attempts to intervene immunologically in cervical cancer.
Affiliation:
Cancer Research Campaign Department of Immunology, Paterson Institute for Cancer Research, Manchester, UK.
Citation:
Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression. 1995, 72 (2):405-11 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Aug-1995
URI:
http://hdl.handle.net/10541/99451
PubMed ID:
7640226
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKeating, P Jen
dc.contributor.authorCromme, F Ven
dc.contributor.authorDuggan-Keen, Margaret Fen
dc.contributor.authorSnijders, P Jen
dc.contributor.authorWalboomers, Jan Men
dc.contributor.authorHunter, Robin Den
dc.contributor.authorDyer, P Aen
dc.contributor.authorStern, Peter Len
dc.date.accessioned2010-05-20T16:06:53Z-
dc.date.available2010-05-20T16:06:53Z-
dc.date.issued1995-08-
dc.identifier.citationFrequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression. 1995, 72 (2):405-11 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid7640226-
dc.identifier.urihttp://hdl.handle.net/10541/99451-
dc.description.abstractThe development of cervical carcinoma is strongly associated with specific types of human papillomaviruses (HPVs). A role for cellular immunity in cervical disease is supported by the increased occurrence of HPV-associated lesions in immunosuppressed individuals. Upon viral infection or malignant transformation, ensuing alterations in gene expression result in the generation of novel sets of peptides which can form complexes with specific HLA class I heavy chains and beta 2-microglobulin. These are then expressed at the cell surface as potential targets for specific T cells. In this study of 100 carcinomas HLA-A and -B class I expression by the tumour cells was down-regulated at one or more alleles in at least 73% of cervical carcinomas. Interference with the transporter associated with antigen presentation (TAP), which translocates cytosolic peptides from endogenously synthesised proteins (e.g. viral) into the lumen of the endoplasmic reticulum was found in 38% of the HLA class I down-regulated tumours. Loss of expression for common HLA class I alleles ranged from 36% to 71%, and such changes might be expected to influence specific immunogenic peptide presentation and consequent immune recognition. These results underline the importance of single as well as multiple allelic loss in cervical neoplasia and have important implications for attempts to intervene immunologically in cervical cancer.en
dc.language.isoenen
dc.subjectUterine Cervical Canceren
dc.subject.meshATP-Binding Cassette Transporters-
dc.subject.meshAdenocarcinoma-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAlleles-
dc.subject.meshBiopsy-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCervix Uteri-
dc.subject.meshDown-Regulation-
dc.subject.meshFemale-
dc.subject.meshGene Deletion-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHLA-A Antigens-
dc.subject.meshHLA-B Antigens-
dc.subject.meshHeterozygote-
dc.subject.meshHumans-
dc.subject.meshMiddle Aged-
dc.subject.meshReference Values-
dc.subject.meshUterine Cervical Neoplasms-
dc.titleFrequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Immunology, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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