Mechanisms of loss of HLA class I expression on colorectal tumor cells.
For several years this laboratory has studied the expression of HLA class I on established colorectal tumor cell lines and on fresh tumors. We review here the mechanisms by which colorectal tumor cells may lose surface expression of HLA class I molecules. Several independent mechanisms have been identified, including loss or mutations in beta 2-microglobulin genes, loss of HLA heavy chain genes, selective lack of expression of HLA alleles, and regulatory defects in HLA expression including loss of expression of the peptide transporters associated with antigen processing (TAP). The data suggest that colorectal tumor cells may evade tumor specific, HLA restricted immune attack by loss of HLA class I expression through a number of mechanisms.
Browning
M
M
ICRF Cancer Immunology Laboratory, John Radcliffe Hospital, Oxford, United Kingdom.
Petronzelli
F
F
Bicknell
D
D
Krausa
P
P
Rowan
A
A
Tonks
S
S
Murray
N
N
Bodmer
J
J
Bodmer
W
W
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured / Q000276:immunology; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000235:genetics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D006680:HLA Antigens; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin