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

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 tr...

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Bibliographic Details
Published in:British journal of cancer 1995-08, Vol.72 (2), p.405-411
Main Authors: KEATING, P. J, CROMME, F. V, DUGGAN-KEEN, M, SNIJDERS, P. J. F, WALBOOMERS, J. M. M, HUNTER, R. D, DYER, P. A, STERN, P. L
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adult
Aged
Aged, 80 and over
Alleles
ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP-Binding Cassette Transporters - genetics
Biological and medical sciences
Biopsy
Carcinoma, Squamous Cell - genetics
Cervix Uteri - physiology
Down-Regulation
Female
Female genital diseases
Gene Deletion
Gene Expression Regulation, Neoplastic
Gynecology. Andrology. Obstetrics
Heterozygote
HLA-A Antigens - genetics
HLA-B Antigens - genetics
Humans
Medical sciences
Middle Aged
Reference Values
Tumors
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - immunology
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1995.346