This dataset contains collected RNASeq data of 552 samples from the GOYA clinical trial. Overall design: The GOYA trial tested the efficacy of Gazyva (GA101) compared with Rituxan (Rituximab) in first line, untreated DLBCL patients. Patients were randomized 1:1 to either G or R combined with a CHOP chemotherapy backbone. Tumor samples were collected at baseline, RNA was isolated using RNA-Access, and RNASeq was run with TruSeq (Illumina) RNASeq.
PD-L1 and tumor-associated macrophages in de novo DLBCL.
Treatment, Subject
View SamplesNatural killer (NK) cells can be divided into phenotypic subsets based on the expression of receptors that bind self-MHC-I molecules with differing affinities; a concept termed licensing or education. Here we show that NK cell subsets exhibit markedly different migratory, effector, and immunoregulatory functions on dendritic cells and antigen-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells preferentially trafficked to draining lymph nodes and produced GM-CSF, which promoted the expansion and activation of dendritic cells, and ultimately resulted in sustained antigen-specific CD8+ T cell responses. In contrast, licensed NK cells preferentially migrated to infected parenchymal tissues and produced greater levels of interferon- (IFN-). Importantly, human NK cell subsets exhibited similar phenotypic characteristics and patterns of cytokine production. Collectively, our studies demonstrate a critical demarcation between the functions of licensed and unlicensed NK cell subsets, with the former functioning as the classical effector subset in inflamed tissues and the latter as modulators of adaptive immunity helping to prime immune responses in draining lymph nodes.
Licensing delineates helper and effector NK cell subsets during viral infection.
Specimen part
View SamplesTreatment of severely refractory Crohns disease (CD) patients remains a clinical challenge. Recent studies show efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however the mechanisms are incompletely understood. We followed a group of patients (n=18) receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy we compared the immunological changes induced by HSCT in responders and non-responders.
Differences in peripheral and tissue immune cell populations following hematopoietic stem cell transplantation in Crohn's disease patients.
Sex, Age, Specimen part, Disease, Time
View SamplesTreatment of severely refractory Crohn's disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy, we studied changes in the immune cell composition in tissue induced by HSCT. Overall design: Biopsy mRNA profiles of 14 CD patients undergoing HSCT were generated by deep sequencing, using HiSeq-4000 platform (Illumina, San Diego, CA).
Differences in Peripheral and Tissue Immune Cell Populations Following Haematopoietic Stem Cell Transplantation in Crohn's Disease Patients.
Sex, Specimen part, Disease, Subject
View SamplesThe v-erbA oncogene belongs to a superfamily of transcription factors called nuclear receptors, which includes the retinoic acid receptors (RARs) responsible for mediating the effects of retinoic acid (RA). Nuclear receptors bind to specific DNA sequences in the promoter region of target genes and v-erbA is known to exert a dominant negative effect on the activity of the RARs. The repressor activity of v-erbA has been linked to the development of hepatocellular carcinoma (HCC) in a mouse model. We have used microarray analysis to identify genes differentially expressed in hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to RA. We have found that v-erbA can affect expression of RA-responsive genes. We have also identified a number of v-erbA-responsive genes that are known to be involved in carcinogenesis and which may play a role in the development of HCC.
Modulation of expression of RA-regulated genes by the oncoprotein v-erbA.
Specimen part, Cell line
View SamplesEffects of the prop-1 and Ghrhr mutations in gene expression during normal aging in mice.
Gene expression profile of long-lived Ames dwarf mice and Little mice.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesGender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice.
Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice.
Sex, Age, Specimen part
View SamplesWe compared gene expression profiles of aire-deficient and wild-type littermate thymic medullary epithelial cells. This was done in order to determine whether Aire's effects differed among strains, and also among individuals of the same strain.
The variable immunological self: genetic variation and nongenetic noise in Aire-regulated transcription.
Sex
View SamplesWe compared gene expression profiles of lymphotoxin alpha- and lymphtoxin beta receptor-deficient thymic medullary epithelial cells with their wild-type littermates, as well as with Aire-deficient and wild-type littermates. This was done in order to determine whether there was overlap in the effects of lymphotoxin and aire.
Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected.
Sex
View SamplesCancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. In this study, we identify a nuclear hormone receptor (ER)-protein kinase (ERK5)-cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor-mediated transcription. Using dominant negative and constitutively active forms, as well as small molecule inhibitors of ERK5 and MEK5, we show that hormone activation of estrogen receptor- determines the nuclear versus cytoplasmic localization of the MAPK family member ERK5, which functions as a coregulator of ER-gene transcription.
Novel roles for ERK5 and cofilin as critical mediators linking ERα-driven transcription, actin reorganization, and invasiveness in breast cancer.
Specimen part
View Samples