Intravesical BCG Immunotherapy is the standard of care in treating non-muscle invasive bladder cancer, yet its mechanism of action remains elusive. Both innate and adaptive immune responses have been implicated in BCG activity. While prior research has indirectly demonstrated the importance of T cells and shown a rise in CD4+ T cells in bladder tissue after BCG, T cell subpopulations have not been fully characterized. We investigated the relationship between effector and regulatory T cells in an immune competent, clinically relevant rodent model of bladder cancer. Our data demonstrate that cancer progression in the MNU rat model of bladder cancer is characterized by a decline in the CD8/FoxP3 ratio, consistent with decreased adaptive immunity. By contrast, treatment with intravesical BCG leads to a large, transient rise in the CD4+ T cell population in the urothelium, and is both more effective and immunogenic compared to intravesical chemotherapy. Interestingly, whole transcriptome expression profiling of post-treatment intravesical CD4+ and CD8+ T cells revealed minimal differences in gene expression after BCG treatment. Together, our results suggest that while BCG induces T cell recruitment to the bladder, the T cell phenotype does not markedly change, implying that combining T cell activating agents with BCG might improve clinical activity.
Intravesical BCG Induces CD4<sup>+</sup> T-Cell Expansion in an Immune Competent Model of Bladder Cancer.
Specimen part, Treatment
View SamplesHuman cytomegalovirus induces a pro-inflammatory monocyte following infection and we have evidence that NF-B and phosphatidylinositol 3-kinase [PI(3)K] are key mediators in this early activation. To begin to address how these signalling pathways are responsible for the rapid activation of infected monocytes, we examined the role these pathways played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes, including inflammatory genes, were regulated in a NF-B- and/or PI(3)K-dependent manner, identifying these pathways as key cellular control points in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection.
Transcriptome analysis of NF-kappaB- and phosphatidylinositol 3-kinase-regulated genes in human cytomegalovirus-infected monocytes.
Specimen part
View SamplesHuman cytomegalovirus induces a pro-inflammatory monocyte following infection. To begin to address how HCMV induces these rapid changes in infected monocytes, we examined the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of pro-inflammatory genes were upregulated within 4 hours post infection.
Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ets transcription factor GABP controls T cell homeostasis and immunity.
Specimen part
View SamplesEts family transcription factor GA-binding protein (GABP) regulates gene expression in CD4 and CD8 T cells.
Ets transcription factor GABP controls T cell homeostasis and immunity.
Specimen part
View SamplesLong recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an alternatively activated phenotype. TAM differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.
The cellular and molecular origin of tumor-associated macrophages.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.
Specimen part, Treatment
View SamplesIdentification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma.
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.
Specimen part, Treatment
View SamplesIdentification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma.
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.
Specimen part
View SamplesThrough development of an in vivo orthotopic lung cancer model, we reveal an unanticipated pathway driving spontaneous metastasis that is orchestrated by the developmentally-regulated transcriptional repressor, Capicua (CIC). Overall design: RNAseq and DNA copy number analysis of H1975 (EGFR-mutant lung adenocarcinoma) cells in the context of drug resistance to rociletinib
Inactivation of Capicua drives cancer metastasis.
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