CD8+ T cells activated by cancer immunotherapy execute tumor clearance mainly by inducing cell death through perforin-granzyme- and Fas/Fas ligand-pathways. Ferroptosis is a form of cell death that differs from apoptosis and results from iron-dependent lipid peroxide accumulation. Although it was mechanistically illuminated in vitro, emerging evidence has shown that ferroptosis may be implicated in a variety of pathological scenarios. However, the involvement of ferroptosis in T cell immunity and cancer immunotherapy is unknown. Here, we find that immunotherapy-activated CD8+ T cells enhance ferroptosis-specific lipid peroxidation in tumor cells, and in turn, increased ferroptosis contributes to the anti-tumor efficacy of immunotherapy. Mechanistically, IFNg released from CD8+ T cells downregulates expression of SLC3A2 and SLC7A11, two subunits of glutamate-cystine antiporter system xc-, restrains tumor cell cystine uptake, and as a consequence, promotes tumor cell lipid peroxidation and ferroptosis. In preclinical models, depletion of cyst(e)ine by cyst(e)inase in combination with checkpoint blockade synergistically enhances T cell-mediated anti-tumor immunity and induces tumor cell ferroptosis. Thus, T cell-promoted tumor ferroptosis is a novel anti-tumor mechanism. Targeting tumor ferroptosis pathway constitutes a therapeutic approach in combination with checkpoint blockade. Overall design: Human HT-1080 mRNA profiles treated by IFNg for 8 hours was determined by RNA-Seq.
CD8<sup>+</sup> T cells regulate tumour ferroptosis during cancer immunotherapy.
Specimen part, Cell line, Treatment, Subject
View SamplesWe used microarrays to provide a transcriptomic signature of different types of cholestasis evoked by 3 different drugs and obstructive surgery
Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury.
Specimen part, Cell line, Treatment
View SamplesTotal RNA extracted from Phytophthora sojae (strain P6497) and infected soybean hypocotyls (cultivar Harosoy) provided template for synthesis of cDNA probes used in the microarray hybridizations. Infected plant hypocotyls were sampled 6 h, 12 h, 24 h, and 48 h after inoculation. Mycelia were grown on synthetic media (H&S) or vegetable juice media (V8). Zoospores were sampled at 0 h, 2 h and 6 h after inducing encystment and germination by agitation.
The Phytophthora sojae avirulence locus Avr3c encodes a multi-copy RXLR effector with sequence polymorphisms among pathogen strains.
Specimen part, Time
View SamplesMesenchymal stromal cells (MSCs) are multipotent stem cells with potent immunosuppressive and trophic support functions. Although bone marrow is considered the golden standard to isolate classical MSCs (BM-MSC), MSC-like cells are currently also derived from other, more easily accessible extra-embryonic tissues such as the umbilical cord. In this study we compared the gene expression profile of human Wharton's jelly explant-derived MSC cultures with two adult MSC populations derived from bone marrow, namely BM-MSC and multipotent adult progenitor cells (MAPC).
Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells.
Specimen part
View SamplesAdult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated single cell transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from
Tubuloids derived from human adult kidney and urine for personalized disease modeling.
Specimen part, Subject
View SamplesAdult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from
Tubuloids derived from human adult kidney and urine for personalized disease modeling.
Specimen part, Subject
View SamplesInhibition of the costimulatory CD40-CD40L receptor/ligand dyad drastically reduces atherosclerosis. However, its long-term blockage can result in immune suppression. We recently identified small molecule inhibitors that block the interaction between CD40 and TNF Receptor Associated Factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity. Here we further characterized the working mechanisms of TRAF-STOPs 6877002 and 6860766 in atherogenesis.
Targeting CD40-Induced TRAF6 Signaling in Macrophages Reduces Atherosclerosis.
Specimen part, Treatment
View Samples