Loss of expression of antigen-presenting molecules in human pancreatic cancer and pancreatic cancer cell lines.
Tumours evade immune recognition and destruction through loss or down-regulation of expression of antigen processing and antigen-presenting molecules such as the human leucocyte antigen (HLA class I) and transporter for antigen presentation (TAP). This study examined the expression of HLA class I, class II and TAP in human pancreatic carcinoma tissue and 19 immortalized pancreatic cancer lines using a panel of antibodies directed against allele-specific as well as monomorphic determinants of these molecules. In tissue samples, reduction or loss of HLA class I and TAP was observed in 76% of cases, loss or down-regulation of TAP expression in 53%. In pancreatic cell lines down-regulation or loss of class I and TAP expression was also observed frequently. However, reductions in class I and TAP expression were reversible upon exposure to interferon-gamma in vitro, suggesting a regulatory rather than structural defect in these genes. De novo class II expression was observed in 26% of tumours and 42% of cell lines and may reflect the differentiation status of the cells. The high rate of class I and TAP loss has implications for immunotherapy strategies for pancreatic cancer, as such changes could facilitate a selective growth advantage for malignant cells. However, the reinduction of expression of these molecules with cytokines such as interferon-gamma may ultimately allow their cytotoxic T cell-mediated destruction.
Pandha
H
H
Department of Oncology, Postgraduate Medical School, University of Surrey, Daphne Jackson Road, Guildford, Surrey GU2 7WG, UK. h.pandha@surrey.ac.uk
Rigg
A
A
John
J
J
Lemoine
N
N
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D009363:Neoplasm Proteins; C477327:transporter associated with antigen processing (TAP)