Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis.
To identify tumor antigens useful for diagnosis and immunotherapy of patients with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA library made from 5 pancreatic cancer cell lines and sera obtained from 8 patients with pancreatic cancer, and isolated total 32 genes, including 14 previously characterized genes and 18 genes with unknown functions. Among these isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair enzymes, Homo sapiens mutS homolog 2 (hMSH2) and Homo sapiens postmeiotic segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as CD4+ helper T cell antigens for immunotherapy of pancreatic cancer patients and that serum IgG antibodies may be useful for diagnosis of patients with pancreatic ductal adenocarcinoma and DM/PM.
Okada
Takaho
T
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Noji
Shinobu
S
Goto
Yasufumi
Y
Iwata
Takashi
T
Fujita
Tomonobu
T
Okada
Tsutomu
T
Matsuzaki
Yuriko
Y
Kuwana
Masataka
M
Hirakata
Michito
M
Horii
Akira
A
Matsuno
Seiki
S
Sunamura
Makoto
M
Kawakami
Yutaka
Y
D000230:Adenocarcinoma / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D003882:Dermatomyositis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D017285:Polymyositis / Q000235:genetics*; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014158:Transcription, Genetic
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C088996:PMS1 protein, human; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein