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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-14
pubmed:abstractText
As pre-existent immunity might be a reflection of an emerging anticancer response, the demonstration of spontaneous T-cell responses against tumor associated antigens (TAAs) in cancer patients may be beneficial before clinical development of dendritic cell (DC)-based cancer vaccines, because it will help to identify likely responders to TAAs among patients who qualify and may benefit from this form of immune therapy. This study aimed to determine pre-existent T-cell reactivity against the tumor suppressor protein p53 in breast cancer patients (BCP) at the time point of primary diagnosis. After a short-term stimulation with autologous wt p53 mRNA-transfected DCs, IFN-? enzyme-linked immunosorbent spot (ELISPOT) analysis revealed p53-reactive T cells in the peripheral blood of more than 40% (15 of 36) of the tested patients. Both CD4(+) and CD8(+) p53-specific T cells secreted IFN-? after stimulation with p53-transfected DCs. Interestingly, more than 72% (13 of 18) of patients with high p53 (p53(high)) expression in tumors were able to mount a p53-specific IFN-? T-cell response, in contrast to only 10% (1 of 10) of healthy donors and 11% (2 of 18) of patients with low or absent p53 (p53(low)) expression in tumors. Furthermore, significantly higher secretion of IL-2 was detected in peripheral blood mononuclear cells after stimulation with p53-transfected DCs from patients with p53(high) tumor expression compared to patients with p53(low) tumor expression, whereas secretion of IL-10 was predominant in the latter group. The high frequency of spontaneous wt p53-reactive T cells detected in the peripheral blood of primary BCP with accumulation of p53 in tumor provides a rationale to consider DCs transfected with mRNA encoding wt p53 for clinical investigation in these patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1573-7217
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
125
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
395-406
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
High immunogenic potential of p53 mRNA-transfected dendritic cells in patients with primary breast cancer.
pubmed:affiliation
Center for Cancer Immune Therapy (CCIT), Department of Hematology, University Hospital Herlev, Copenhagen, 2730, Herlev, Denmark. ozcmet01@heh.regionh.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't