Document Detail


Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine.
MedLine Citation:
PMID:  23226513     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma (mRCC) who received combined treatment with IL-2, interferon-?-2a and dendritic cell vaccine. We examined gene expression, cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry (FCM). Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors (HD). PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and T(REG)-cell activation pathways, which was also reflected in lymphocyte subset distribution. Overall, PBL gene expression post-treatment (POST) was not significantly different than pre-treatment (PRE). Nevertheless, treatment related changes in gene expression (post-treatment minus pre-treatment) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding (R) patients compared to non-responding (NR) patients. In addition, we observed down-regulation of T(REG)-cell pathways post-treatment in R vs. NR patients. While exploratory in nature, this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy. This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC.
Authors:
Benita Wolf; Adrian Schwarzer; Anik L Côté; Thomas H Hampton; Thomas Schwaab; Eduardo Huarte; Craig R Tomlinson; Jiang Gui; Jan L Fisher; Camilo E Fadul; Joshua W Hamilton; Marc S Ernstoff
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-03
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-12-11     Completed Date:  2013-06-11     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e50221     Citation Subset:  IM    
Affiliation:
Medical Oncology Immunotherapy Group, Section of Hematology/Oncology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, United States of America.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE34465
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MeSH Terms
Descriptor/Qualifier:
Cancer Vaccines / therapeutic use*
Carcinoma, Renal Cell / blood,  genetics*,  therapy
Cluster Analysis
Cytokines / blood
Dendritic Cells / immunology*
Female
Flow Cytometry
Gene Expression Profiling*
Humans
Interferon-alpha / therapeutic use*
Interleukin-2 / therapeutic use*
Kidney Neoplasms / blood,  genetics*,  therapy
Lymphocyte Subsets
Lymphocytes / metabolism*
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
P20 RR016437/RR/NCRR NIH HHS; P20RR016437/RR/NCRR NIH HHS; P30 CA023108/CA/NCI NIH HHS; P30CA023108/CA/NCI NIH HHS; R01 CA095648/CA/NCI NIH HHS; R01 CA5648/CA/NCI NIH HHS; R21 CA112761/CA/NCI NIH HHS; R21CA112761/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cancer Vaccines; 0/Cytokines; 0/Interferon-alpha; 0/Interleukin-2
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