Linked Life Data

16322265

Source:http://linkedlifedata.com/resource/pubmed/id/16322265

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2005-12-2
pubmed:abstractText
Human papillomavirus (HPV)-associated squamous cell carcinoma of the head and neck (SCCHN) seems to be a suitable target for cancer vaccination. HPV-encoded oncogenic proteins, such as E7, are promising tumor-specific antigens and are obligatory for tumor growth. Because few immunologic studies have analyzed the endogenous HPV-specific immune response in this subset of SCCHN patients, we studied T-cell frequencies against HPV-16 E7(11-20) or E7(86-93) in tumor-bearing, human leukocyte antigen (HLA)-A*0201+ SCCHN patients, whose tumors were either HPV-16+ or HPV-16-. In HPV-16+ SCCHN patients, frequencies of T cells against either peptide were significantly elevated (P < 0.005) compared with HPV-16- patients or healthy volunteers. Tetramer+ T cells showed evidence of terminally differentiated phenotype (CD45RA+CCR7-) and an elevated level of CD107a staining for degranulation. Despite detectable expression of the restricting HLA class I allele, HLA-A*0201-E7(11-20)- or HLA-A*0201-E7(86-93)-specific CTL obtained by in vitro stimulation of healthy donor peripheral blood mononuclear cells only recognize a naturally HPV-16-transformed, HLA-A*0201+ SCCHN cell line after pretreatment with IFN-gamma. This cell line had little or no expression of LMP2, TAP1, and tapasin, critical components of the HLA class I antigen-processing machinery, which were up-regulated by IFN-gamma treatment. Immunohistochemistry of HPV-16+ SCCHN tumors showed that these antigen-processing machinery components are down-regulated in tumors in vivo compared with adjacent normal squamous epithelium. Thus, immunity to HPV-16 E7 is associated with the presence of HPV-16 infection and presentation of E7-derived peptides on SCCHN cells, which show evidence of immune escape. These findings support further development of E7-specific immunotherapy and strategies for up-regulation of antigen-processing machinery components in HPV-associated SCCHN.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11146-55
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16322265-Animals, pubmed-meshheading:16322265-Carcinoma, Squamous Cell, pubmed-meshheading:16322265-Dendritic Cells, pubmed-meshheading:16322265-Epitopes, T-Lymphocyte, pubmed-meshheading:16322265-HLA-A Antigens, pubmed-meshheading:16322265-HLA-A2 Antigen, pubmed-meshheading:16322265-Head and Neck Neoplasms, pubmed-meshheading:16322265-Human papillomavirus 16, pubmed-meshheading:16322265-Humans, pubmed-meshheading:16322265-Immunotherapy, Adoptive, pubmed-meshheading:16322265-Interferon-gamma, pubmed-meshheading:16322265-Male, pubmed-meshheading:16322265-Mice, pubmed-meshheading:16322265-Mice, Transgenic, pubmed-meshheading:16322265-Oncogene Proteins, Viral, pubmed-meshheading:16322265-Papillomavirus E7 Proteins, pubmed-meshheading:16322265-Papillomavirus Infections, pubmed-meshheading:16322265-T-Lymphocytes, Cytotoxic
pubmed:year
2005
pubmed:articleTitle
Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck.
pubmed:affiliation
Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural