Specific T-cell immunity against Ki-ras peptides in patients with pancreatic and colorectal cancers.
Mutations of codon 12 in the Ki-ras gene are frequently found in pancreatic and colorectal cancers. It has been demonstrated that human T-cells have the potential to recognise tumours expressing mutated ras-derived peptides. However, it remains unclear whether T-cells from a given individual can recognise the mutant peptides, which are expressed in that individual's tumour tissues. Mutations of the Ki-ras oncogene were analysed by the mutant-allele-specific amplification (MASA) method in pancreatic and colorectal tumour tissues, and T-cell responses against mutated Ki-ras-derived peptides were measured by [(3)H]thymidine incorporation and IFN-gamma production assays. Specific T-cell responses against Ki-ras-products were found in cancer patients, whereas no immune response was observed in normal individuals (P<0.01). Six of the eight pancreatic cancer patients (75%) and nine of 26 colorectal cancer patients (35%) had T-cell responses to mutated Ki-ras-derived-peptides. T-cell response in a given individual cannot recognise the same mutated ras peptide, which is expressed in that individual's tumour tissues. However, pancreatic and colorectal cancer patients have T-cell immunity against Ki-ras-peptides, and this provides potential target for cancer immunotherapy.
Shono
Y
Y
Second Department of Surgery, Wakayama Medical University, School of Medicine, Japan.
Tanimura
H
H
Iwahashi
M
M
Tsunoda
T
T
Tani
M
M
Tanaka
H
H
Matsuda
K
K
Yamaue
H
H
D002455:Cell Division; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D016283:Proto-Oncogene Proteins p21(ras); D013601:T-Lymphocytes / Q000276:immunology*; D018631:ras Proteins
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D007371:Interferon-gamma; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins