Loss of human leukocyte antigen expression on colorectal tumor cell lines: implications for anti-tumor immunity and immunotherapy.
A system devised for tissue typing the human leukocyte antigen-A (HLA-A) locus from genomic DNA by the polymerase chain reaction (PCR) has been used to investigate abnormalities of HLA expression in a panel of 30 cell lines derived from colorectal adenocarcinomas, by comparison of the HLA-A locus genotype with surface expression of HLA. Eleven cell lines gave single HLA-A locus specificity on PCR typing, suggesting that loss of HLA alleles is a common abnormality. In one of these cell lines the loss of an HLA-A locus allele was confirmed by comparison with DNA from a lymphoblastoid B cell line derived from the same patient. In three cell lines, loss of expression of an HLA-A locus determinant was observed in spite of the presence of the relevant allele in genomic DNA. Three cell lines showed absent HLA expression associated with failure to express beta 2-microglobulin. These data indicate that at least three independent mechanisms were involved in the loss of HLA expression on the colorectal tumor cell lines.
Browning
M J
MJ
ICRF, Cancer Immunology Laboratory, John Radcliffe Hospital, Oxford, England.
Krausa
P
P
Rowan
A
A
Hill
A B
AB
Bicknell
D C
DC
Bodmer
J G
JG
Bodmer
W F
WF
D000954:Antigens, Surface / Q000032:analysis; D002874:Chromosome Mapping; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D016678:Genome; D005838:Genotype; D006680:HLA Antigens / Q000032:analysis*; D015234:HLA-A Antigens / Q000235:genetics; D015789:HLA-A2 Antigen / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007167:Immunotherapy; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D006680:HLA Antigens; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I