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T cell receptor repertoire profiling of murine skin transplantation in context of PD-1+ cells Ablation therapy

ABSTRACT: T cell receptor repertoire profiling of murine skin transplantation in context of PD-1+ cells Ablation therapy

PROVIDER: PRJNA896559 | ENA |

REPOSITORIES: ENA

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T cell receptor repertoire profiling of murine skin transplantation in context of PD-1+ cells Ablation therapy

Project description:The purpose of this study was to evaluate the influence of ablating PD-1+ cells on alloreactive T cell repertoires. We established the murine skin transplantation model and obtained the draining lymph nodes (dLNs) T cells from recipients for TCR repertoires sequencing.

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Specific ablation of PD-1 on regulatory T cells promotes antitumor immunity

Project description:Regulatory T cells (Tregs) have an immunosuppressive function and highly express PD-1 in tumor microenvironment, but the function of PD-1 in Tregs is still controversial. Using murine tumor model, we demonstrated that Tregs-specific PD-1 conditional Knock-Out mice are resistant to tumor progression. Using PD-1 hetero conditional Knock-Out mice in which both PD-1 expressing Tregs and deficient Tregs co-exist, we found that specific ablation of PD-1 on Tregs results in impaired proliferative capacity and functionality of Tumor-infiltrating Tregs. Single cell RNA and VDJ sequencing revealed that PD-1 signaling in TI Tregs induces global transcriptome crucial for Tregs homeostasis and functionality. Taken together, we suggest that specific ablation of PD-1 on Tregs promotes antitumor immunity by exacerbating Tregs stability and functionality.

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ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation

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Single-Cell Analysis of Transcriptome and TCR Sequencing Reveals Immune Cell Atlas and Functional Heterogeneity of T Cell Repertoire in Murine Heart Transplantation

Project description:To illustrate the immune cell atlas and functional heterogeneity of T cell repertoire in murine heart transplantation，we established the murine heterotopic heart transplantation model and isolated CD45 positive cells from cardiac grafts and spleens for single cell transcriptome and TCR sequencing.

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Gene expression profile of mouse breast cancer V720 cells treated with vehicle or PD 0332991

Project description:D-cyclins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment, we engineered mouse strains which allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D associated kinase activity in mice bearing ErbB2-driven mammary carcinomas halted cancer progression and triggered tumor-specific senescence, without compromising the animals' health. Ablation of cyclin D3 in mice bearing T-cell acute lymphoblastic leukemias (T-ALL) triggered tumorspecific apoptosis. Such selective killing of leukemic cells can be also achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Hence, contrary to what one might expect from ablation of a cell cycle protein, acute shutdown of a D-cyclin leads not only to cell cycle arrest, but it also triggers tumor cell senescence or apoptosis, and it affects different tumor types through distinct cellular mechanisms. Inhibiting cyclin D-activity represents a highly-selective anticancer strategy which specifically targets cancer cells without significantly affecting normal tissues. Mouse breast cancer V720 cells were cultured in the presence of the CDK4/6 inhibitor PD 0332991 (PD; 1 microM) or vehicle (VO) for 24 hrs. Experiment was done in biological triplicate. A total of 6 RNA samples (3 vehicle treated and 3 PD 0332991 treated samples) were used for microarray expression analysis.

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