Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-11-1
pubmed:abstractText
Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2006 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2851-60
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16998881-Aged, pubmed-meshheading:16998881-Aged, 80 and over, pubmed-meshheading:16998881-Antibodies, pubmed-meshheading:16998881-Antigens, CD3, pubmed-meshheading:16998881-CD8-Positive T-Lymphocytes, pubmed-meshheading:16998881-Carcinoma, Hepatocellular, pubmed-meshheading:16998881-Dimerization, pubmed-meshheading:16998881-Epitopes, pubmed-meshheading:16998881-Female, pubmed-meshheading:16998881-Flow Cytometry, pubmed-meshheading:16998881-HLA-A2 Antigen, pubmed-meshheading:16998881-Humans, pubmed-meshheading:16998881-Immunophenotyping, pubmed-meshheading:16998881-Immunotherapy, pubmed-meshheading:16998881-Liver Neoplasms, pubmed-meshheading:16998881-Male, pubmed-meshheading:16998881-Middle Aged, pubmed-meshheading:16998881-Peptide Fragments, pubmed-meshheading:16998881-T-Lymphocytes, Cytotoxic, pubmed-meshheading:16998881-Tumor Suppressor Protein p53
pubmed:year
2006
pubmed:articleTitle
Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma.
pubmed:affiliation
Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany. vito.cicinnati@uni-due.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural