Project description:We investigated whether exogenous supplies of different IL-2R agonists (IL-2wt, IL-2nα or IL-2α-bias) at the concentration of 3 mg/g body weight could rescue the transcriptional signatures of dysfunctional T cells in large tumors, or allow them to regain sensitivity to αPD-1 antibody. Remarkably, after transient stimulation by IL-2wt, large tumors fully restored the effector/activation signatures observed in small tumors, such as upregulation of effector genes (Gzma, Gzmb, Gzmk and Ifng), T cell activation/exhaustion genes (Ctla4, Pdcd1, Lag3 and Havcr2), inflammatory cytokine/cytokine receptors (Il2ra, Il2rb, Il2rg and Il21r), and chemokines (Cxcl9, Cxcl10 and Ccl19) (Fig.7d). Surprisingly, although IL-2α-bias had >10-fold weaker in vitro activity than IL-2wt, and could only activate the small fraction of CD25-upregulated CD8+Teff cells, the transcriptional profiles were indistinguishable between IL-2wt and IL-2α-bias treated large tumors. In stark contrast, IL-2nα treatment showed no meaningful transcriptional changes in large tumors compared to untreated control. These results once again demonstrate the critical role of CD25 in transmitting IL-2 signaling to reprogram the tumor immune microenvironment.
Project description:To investigate the mechanism by which 25-HC restricts cytotoxic T cell differentiation, we performed RNA-seq on 25-HC-treated CD8+ T cells.Total RNA was extracted from activated CD8+ T cells, treated with 250 nM 25-HC or DMSO, using TRIzol reagent.
Project description:A mouse model of patient-derived glioma tissue was used to explore the relationship between transcriptome alterations and tissue stiffness.
Project description:Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant glioma. Oncolytic adenoviruses are being modified to exploit the aberrant expression of proteins in tumor cells to enhance tumor tropism and glioma-selective replication. E1A mutant adenovirus Delta-24-RGD has shown favorable toxicity profile and remarkable efficacy in a first-in-human phase I clinical trial. However, the comprehensive modulation of glioma metabolism in response to Delta-24-RGD infection is poorly understood. Integrating mass spectrometry based-quantitative proteomics, physical and functional interaction data, and biochemical approaches, we conducted a cell-wide study of cytosolic, nuclear, and secreted glioma proteomes throughout the early time course of Delta-24-RGD infection.
Project description:Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant glioma. Oncolytic adenoviruses are being modified to exploit the aberrant expression of proteins in tumor cells to enhance tumor tropism and glioma-selective replication. E1A mutant adenovirus Delta-24-RGD has shown favorable toxicity profile and remarkable efficacy in a first-in-human phase I clinical trial. However, the comprehensive modulation of glioma metabolism in response to Delta-24-RGD infection is poorly understood. Integrating mass spectrometry based-quantitative proteomics, physical and functional interaction data, and biochemical approaches, we conducted a cell-wide study of intracellular and secreted glioma proteomes at late stage of Delta-24-RGD infection, when prominent autophagy has been described.
Project description:Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant glioma. Oncolytic adenoviruses are being modified to exploit the aberrant expression of proteins in tumor cells to enhance tumor tropism and glioma-selective replication. E1A mutant adenovirus Delta-24-RGD has shown favorable toxicity profile and remarkable efficacy in a first-in-human phase I clinical trial. However, the comprehensive modulation of glioma metabolism in response to Delta-24-RGD infection is poorly understood. Integrating mass spectrometry based-quantitative proteomics, physical and functional interaction data, and biochemical approaches, we conducted a cell-wide study of intracellular and secreted glioma proteomes at late stage of Delta-24-RGD infection, when prominent autophagy has been described.
Project description:We sequenced total 10 virus infected mouse hippocampus: 3 samples of lentivirus infected, 4 samples of 1st batch retrovirus infected as batch A, and 3 samples as batch B retrovirus infected. Examination of mRNA levels using TU-tagging approach that differ the newborn neurons from mature neurons.
Project description:Intensive usage of cancer cell lines as cellular model system in cancer research caused the generation of variant subtypes during the last decades. This study focused on the human leukemic THP-1 cell line as a monocyte model. THP-1 cells from two different depositors were differentiated into various immune states. Additionally primary immune cells were differentiated into various immune states in order to be a comparative dataset.