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rdf:type |
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lifeskim:mentions |
umls-concept:C0022702,
umls-concept:C0031437,
umls-concept:C0042196,
umls-concept:C0205263,
umls-concept:C0221784,
umls-concept:C0231174,
umls-concept:C0597535,
umls-concept:C0871261,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
26
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pubmed:dateCreated |
2010-7-9
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|
pubmed:abstractText |
One half of a group of 20 patients with human papillomavirus type 16 (HPV16)-induced vulvar intraepithelial neoplasia grade 3 displayed a complete regression (CR) after therapeutic vaccination with HPV16 E6/E7 synthetic long peptides. Patients with relatively larger lesions generally did not display a CR. To investigate immune correlates of treatment failure, patients were grouped according to median lesion size at study entry, and HPV16-specific immunity was analyzed at different time points by complementary immunological assays. The group of patients with smaller lesions displayed stronger and broader vaccine-prompted HPV16-specific proliferative responses with higher IFNgamma (P = 0.0003) and IL-5 (P < 0.0001) levels than patients with large lesions. Characteristically, this response was accompanied by a distinct peak in cytokine levels after the first vaccination. In contrast, the patient group with larger lesions mounted higher frequencies of HPV16-specific CD4(+)CD25(+)Foxp3(+) T cells (P = 0.005) and displayed a lower HPV16-specific IFNgamma/IL-10 ratio after vaccination (P < 0.01). No disparity in T memory immunity to control antigens was found, indicating that the differences in HPV-specific immunity did not reflect general immune failure. We observed a strong correlation between a defined set of vaccine-prompted specific immune responses and the clinical efficacy of therapeutic vaccination. Notably, a high ratio of HPV16-specific vaccine-prompted effector T cells to HPV16-specific CD4(+)CD25(+)Foxp3(+) T cells was predictive of clinical success. Foxp3(+) T cells have been associated previously with impaired immunity in malignancies. Here we demonstrate that the vaccine-prompted level of this population is associated with early treatment failure.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
|
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:Berends-van der MeerDorien M ADM,
pubmed-author:DrijfhoutJan WJW,
pubmed-author:EssahsahFarahF,
pubmed-author:FathersLorraine MLM,
pubmed-author:FleurenGert JanGJ,
pubmed-author:FrankenKees L M CKL,
pubmed-author:KenterGemma GGG,
pubmed-author:LöwikMargriet J GMJ,
pubmed-author:MeliefCornelis J MCJ,
pubmed-author:OostendorpJaapJ,
pubmed-author:PiersmaSytse JSJ,
pubmed-author:RamwadhdoebeTamara HTH,
pubmed-author:StynenboschLinda F MLF,
pubmed-author:ValentijnA Rob P MAR,
pubmed-author:VloonAnnelies P GAP,
pubmed-author:WeltersMarij J PMJ,
pubmed-author:de Vos van SteenwijkPeggy JPJ,
pubmed-author:van der BurgSjoerd HSH,
pubmed-author:van der HulstJeanette MJM
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pubmed:issnType |
Electronic
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pubmed:day |
29
|
|
pubmed:volume |
107
|
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pubmed:owner |
NLM
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|
pubmed:authorsComplete |
Y
|
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pubmed:pagination |
11895-9
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pubmed:dateRevised |
2010-12-30
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pubmed:meshHeading |
pubmed-meshheading:20547850-CD4-Positive T-Lymphocytes,
pubmed-meshheading:20547850-Cancer Vaccines,
pubmed-meshheading:20547850-Carcinoma in Situ,
pubmed-meshheading:20547850-Cytokines,
pubmed-meshheading:20547850-Female,
pubmed-meshheading:20547850-Forkhead Transcription Factors,
pubmed-meshheading:20547850-Human papillomavirus 16,
pubmed-meshheading:20547850-Humans,
pubmed-meshheading:20547850-Interleukin-2 Receptor alpha Subunit,
pubmed-meshheading:20547850-Kinetics,
pubmed-meshheading:20547850-Lymphocyte Activation,
pubmed-meshheading:20547850-Papillomavirus Infections,
pubmed-meshheading:20547850-Papillomavirus Vaccines,
pubmed-meshheading:20547850-Remission Induction,
pubmed-meshheading:20547850-T-Lymphocyte Subsets,
pubmed-meshheading:20547850-T-Lymphocytes,
pubmed-meshheading:20547850-T-Lymphocytes, Regulatory,
pubmed-meshheading:20547850-Treatment Failure,
pubmed-meshheading:20547850-Vulvar Neoplasms
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pubmed:year |
2010
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|
pubmed:articleTitle |
Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses.
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pubmed:affiliation |
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Clinical Trial, Phase II
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