To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN- and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines.
Persistent antigen at vaccination sites induces tumor-specific CD8⁺ T cell sequestration, dysfunction and deletion.
Specimen part, Time
View SamplesAn 11-point time course study comparing V6.5 embryonic stem cells versus embryoid bodies. Time course 0 hours, 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 4 days, 7 days, 9 days, and 14 days.
Gene function in early mouse embryonic stem cell differentiation.
Sex
View SamplesAn 11-point time course study comparing R1 embryonic stem cells versus embryoid bodies. Time course 0 hours, 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 4 days, 7 days, 9 days, and 14 days.
Gene function in early mouse embryonic stem cell differentiation.
Sex
View SamplesAn 11-point time course study on differentiating embryoid bodies from a murine J1 embryonic stem cell line. The time course includes 0 hr, 6 hr, 12 hr, 18 hr, 24 hr, 36 hr, 48 hr, 4 days, 7 days, 9 days and 14 days.
Gene function in early mouse embryonic stem cell differentiation.
Sex
View SamplesGenome-wide association studies (GWAS) have identified 19 risk variants associated with colorectal cancer. As most of these risk variants reside outside the coding regions of genes, we conducted cis-expression quantitative trait loci (cis-eQTL) analyses to investigate possible regulatory functions on the expression of neighboring genes.
cis-Expression QTL analysis of established colorectal cancer risk variants in colon tumors and adjacent normal tissue.
Disease, Disease stage
View SamplesAberrant forms of the SWI/SNF chromatin remodeling complex are associated with human disease. Loss of the Snf5 subunit of SWI/SNF is a driver mutation in pediatric rhabdoid cancers and forms aberrant sub-complexes that are not well characterized. We determined the effects of loss of Snf5 on the composition, nucleosome binding, recruitment and remodeling activities of yeast SWI/SNF. The Snf5 subunit interacts with the ATPase domain of Snf2 and forms a submodule consisting of Snf5, Swp82 and Taf14 as shown by mapping SWI/SNF subunit interactions by crosslinking-mass spectrometry and subunit deletion followed by immunoaffinity chromatography. Snf5 promoted binding of the Snf2 ATPase domain to nucleosomal DNA, enhanced its catalytic activity and facilitated nucleosome remodeling. Snf5 was required for acidic transcription factors to recruit SWI/SNF to chromatin. RNA-seq analysis suggested that both the recruitment and catalytic functions mediated by Snf5 are required for SWI/SNF regulation of gene expression. Overall design: Determining the effects of loss of Snf5 on the composition, nucleosome binding, recruitment, remodeling activities and gene expression profile of yeast SWI/SNF
Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex.
Cell line, Subject
View SamplesThe protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.
MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
Treatment
View SamplesDiffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.
Treatment
View SamplesTranscriptional profiling of genes regulated by PaWRKY1 transcription factor
Characterization of the early response of the orchid, Phalaenopsis amabilis, to Erwinia chrysanthemi infection using expression profiling.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL.
Cell line, Treatment
View Samples