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 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.
Keating
P J
PJ
Cancer Research Campaign Department of Immunology, Paterson Institute for Cancer Research, Manchester, UK.
Cromme
F V
FV
Duggan-Keen
M
M
Snijders
P J
PJ
Walboomers
J M
JM
Hunter
R D
RD
Dyer
P A
PA
Stern
P L
PL
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002584:Cervix Uteri / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D012016:Reference Values; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015234:HLA-A Antigens; D015235:HLA-B Antigens; C073119:TAP1 protein, human