Similar Datasets
Project description:Cancer treatment has been revolutionized by immune checkpoint inhibitors, which regulate immune cell function by blocking the interactions between immune checkpoint molecules and their ligands. The interaction between programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) is a target for immune checkpoint inhibitors. Nanobodies, which are recombinant variable domains of heavy-chain-only antibodies, can replace existing immune checkpoint inhibitors, such as anti-PD-1 or anti-PD-L1 conventional antibodies. However, the screening process for high-affinity nanobodies is laborious and time-consuming. Here, we identified high-affinity anti-PD-1 nanobodies using peptide barcoding, which enabled reliable and efficient screening by distinguishing each nanobody with a peptide barcode that was genetically appended to each nanobody. We prepared a peptide-barcoded nanobody (PBNb) library with thousands of variants. Three high-affinity PBNbs were identified from the PBNb library by quantifying the peptide barcodes derived from high-affinity PBNbs. Furthermore, these three PBNbs neutralized the interaction between PD-1 and PD-L1. Our results demonstrate the utility of peptide barcoding and the resulting nanobodies can be used as experimental tools and antitumor agents. Peptide barcoding can be used to screen for molecules other than nanobodies. Our methods, such as the design of peptide barcodes, the design of peptide-barcoded molecules, preparation of peptide-barcoded molecule library, and quantification of peptide barcodes, are helpful in screening for peptide-barcoded molecules.
2024-03-21 | PXD041000 | JPOST Repository
Project description:Targeting T-cell Lymphoma Epigenome Induces Cell Death, Cancer Testes Antigens, Immune Modulatory Signaling Pathways
| PRJNA622991 | ENA
Project description:Robust transcriptional indicators of plant immune cell death revealed by spatio-temporal transcriptome analyses
| PRJNA813448 | ENA
Project description:While RNA viruses evade host immune responses by perturbing transcriptional and translational machinery, the host organism counteracts viral invasion through activation of regulated cell death pathways. However, the precise molecular mechanisms underlying host-initiated cell death activation in response to viral infection remain poorly characterized. By genome-wide screening, we identified ribosomal protein RPSA as a broad inducer of RNA virus replication-dependent cell death that confers antiviral protection. Rpsa conditional knockout mice exhibited heightened susceptibility to RNA viruses with attenuated cell death activation in infected tissues. Mechanistically, RNA virus infection triggers K29-linked polyubiquitination of RPSA, which strengthens its binding to the helicase domain of NAT10 and potently inhibits NAT10's helicase activity, thereby blocking R-loop resolution. The resulting R-loop accumulation drives DNA damage-mediated cell death execution. Our findings uncover a novel intranuclear "inside-out" R-loop-driven cell death pathway orchestrated by RPSA, providing fresh insights into virus-host interactions and identifying potential therapeutic targets for RNA viral infections.
2025-07-18 | GSE300291 | GEO
Project description:The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. However, most siRNAs or shRNAs targeting either CD95 or CD95L induce DICE (Death Induced by CD95/CD95L Elimination), a form of cell death in which a combination of different cell death pathways are activated, that is selective for transformed cells, and that preferentially affects cancer stem cells. We now provide evidence that both CD95 and CD95L are part of a network of genes that contain sequences that when expressed as either siRNAs or shRNAs are toxic to cancer cells. They act through canonical RNAi by targeting the 3'UTRs of critical survival genes. We propose that these embedded toxic sequences are part of a conserved mechanism that regulates cell death, and we predict the existence of endogenous siRNAs, that when produced, induce cell death to regulate genome fidelity. Our data have implications for cancer therapy and the use of RNAi.
2017-09-16 | GSE101183 | GEO
Project description:Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation
| PRJNA914320 | ENA
Project description:ALK2/3 are components of the immune synapse crucial for T cell activation and death
| PRJNA1238328 | ENA
Project description:A properly functioning immune system is vital for an organism's wellbeing. Immune tolerance is a critical feature of the immune system that allows immune cells to mount effective responses against exogenous pathogens such as viruses and bacteria, while preventing attack to self-tissues. Activation-induced cell death (AICD) in T lymphocytes, in which repeated stimulations of the T-cell receptor (TCR) lead to activation and then apoptosis of T cells, is a major mechanism for T cell homeostasis and helps maintain peripheral immune tolerance. Defects in AICD can lead to development of autoimmune diseases. Despite its importance, the regulatory mechanisms that underlie AICD remain poorly understood, particularly at an integrative network level. Here, we develop a dynamic multi-pathway model of the integrated TCR signalling network and perform model-based analysis to characterize the network-level properties of AICD. Model simulation and analysis show that amplified activation of the transcriptional factor NFAT in response to repeated TCR stimulations, a phenomenon central to AICD, is tightly modulated by a coupled positive-negative feedback mechanism. NFAT amplification is predominantly enabled by a positive feedback self-regulated by NFAT, while opposed by a NFAT-induced negative feedback via Carabin. Furthermore, model analysis predicts an optimal therapeutic window for drugs that help minimize proliferation while maximize AICD of T cells. Overall, our study provides a comprehensive mathematical model of TCR signalling and model-based analysis offers new network-level insights into the regulation of activation-induced cell death in T cells
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
2020-03-20 | MODEL2003200002 | BioModels