Project description:The tumoricidal effects of CD8+T cells are well acknowledged, but how MHC Ib-restricted CD8+T (Ib-CD8+T) cells contribute to anti-tumor immunity remains obscure. Here, we show that infusion of MHC Ia+ cells to Kb-/-Db-/- mice induced the expansion of Ib-CD8+T cells in tumors and potently inhibited tumor progression. Such priming of Ib-CD8+T cells by MHC-Ia is not MHC haplotype restricted and MHC Ia tetramers alone can prime Ib-CD8+T cells for activation. The MHC Ia priming promoted Tbet expression in Ib-CD8+T cells and in absence of Tbet, such priming effect diminished. Importantly, these tumoricidal Ib-CD8+T cells are positive for CX3CR1, and exhibit rapid proliferation, high expression of cytotoxic factors, and prolonged persistence at tumor sites. Adoptive transfer of CX3CR1+Ib-CD8+T cells to wild type mice resulted in potent anti-tumor effects. Our findings unravel an uncharacterized function of MHC Ia molecules in immunoregulation and raise the possibility of using Ib-CD8+T cells in tumor immunotherapy.
Project description:We have previously developed the use of genetically engineered herpes simplex virus type 1 ("G207") for the experimental treatment of malignant glioma (PMID: 18957964). We demonstrated that G207 propagates in and kills nervous system tumor cells with little to no evidence of viral encephalitis. Here, six adult patients with recurrent glioblastoma were recruited onto a phase Ib clinical trial to test G207 safety and efficacy in anti-tumor response. We obtained resected tumor tissue before and after (within 2-5 days) inoculation with G207. RNA was extracted from all tissues and subject to library preparation for RNA sequencing on Illumina instrumentation.
Project description:Global transcriptome analyses provide an excellent basis for the identification and definition of biomarkers with high relevance in infection processes, therapeutic intervention and protective immunity. The measurement applies three different state of the art transcriptomic technologies for global expression profiling to vaccine development. Different microarray platforms in conjunct to next generation sequencing (NGS) will build the basis for comparative approaches, such as up-down classification and correlation coefficients. This measurement is based on Agilent microarrays and a clinical trial phase Ib study with M. bovis BCG vaccination. • Surrogate measurement using whole human blood • 4 time points: d0 (naïve, pre-immunization) and d14, d28,d56, d168 post m. bovis BCG immunization • Responses of PPD positive study groups • Group size of approximately 6 individuals European network of vaccine research and development (TRANSVAC)
Project description:Global transcriptome analyses provide an excellent basis for the identification and definition of biomarkers with high relevance in infection processes, therapeutic intervention and protective immunity. The measurement applies three different state of the art transcriptomic technologies for global expression profiling to vaccine development. Different microarray platforms in conjunct to next generation sequencing (NGS) will build the basis for comparative approaches, such as up-down classification and correlation coefficients. This measurement is based on Agilent microarrays and a clinical trial phase Ib study with M. bovis BCG vaccination. M-bM-^@M-" Surrogate measurement using whole human blood M-bM-^@M-" 4 time points: d0 (naM-CM-/ve, pre-immunization) and d14, d28,d56, d168 post m. bovis BCG immunization M-bM-^@M-" Responses of PPD positive study groups M-bM-^@M-" Group size of approximately 6 individuals European network of vaccine research and development (TRANSVAC) Microarray experiments were performed as single-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays
Project description:B-cell acute lymphoblastic leukemia (B-ALL) is the most prevailing childhood cancer. As predicated by its prenatal origin, infant B-ALL (iB-ALL) show a silent mutational landscape irrespective of the MLL rearrangement/status, suggesting that other regulatory mechanisms might be impaired in the context of the disease. Here we used the most recent Illumina MethylationEPIC Beadchip platform to describe the genome-wide DNA methylation changes observed in a total of 69 de novo MLL-AF4+, MLL-AF9+ and non-rearranged MLL iB-ALL leukemias uniformly treated according to Interfant 99/06 protocol. Please note that samples X8 and X9 (pool of B cells and BCP) correspond to samples 200340580160_R08C01 and 200340580161_R07C01 from study E-MTAB-6315, respectively.
Project description:Series of stage IB lung adenocarcinomas and large cell carcinomas. The aim of the study was to predict outcome using a Copy Number Driven Gene Expression signature. Experiment Overall Design: Homogeneous series of 72 cases of lung primary stage IB adenocarcinomas/large cell carcinomas, analyzed using the Human U133Plus 2.0 oligonucleotide arrays (Affymetrix, Santa Clara, CA).
