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Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer

ABSTRACT: Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer

PROVIDER: PRJNA932262 | ENA |

REPOSITORIES: ENA

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Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [human scRNA]

Project description:Although the de-differentiation process of thyroid cancer has been studied, it remains unclear how T cell antigen receptor (TCR) dynamically changes during the cancer progression and treatment. Here we characterized the γδ TCR repertoire along the de-differentiation of thyroid cancers cross-sectionally and investigated the longitudinal changes of TCR components over time in thyroid cancer patients receiving different treatment. We found that better differentiated status was significantly related to greater diversity and lower clonality. Expanded TCRs show enhanced convergent recombination and improved antigen-driven anti-tumor immune responses. The longitudinal study suggested that post-radiotherapeutic immunotherapy led to favorable clinical outcome, which was attributed to the appearance and expansion of neo clonotypes and was validated by scRNA-seq data and murine model experiment. These findings provided a novel understanding in the progression of thyroid cancer and highlighted the role of γδ T cells in anti-tumor immunity.

2024-12-31 | GSE224719 | GEO

Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [mouse scRNA]

2024-12-31 | GSE224720 | GEO

Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [mouse scRNA]

Project description:Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [mouse scRNA]

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Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [human scRNA]

Project description:Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [human scRNA]

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SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire

Project description:During thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM-SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire. SAP deficiency resulted in both a significant loss of an immatureGzma+Blk+Etv5+Tox2+γδT17 precursor population, and a significant increase inCd4+Cd8+Rorc+Ptcra+Rag1+thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data suggest that SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire.

2024-07-08 | GSE262064 | GEO

γδ-T cells and αβ-TCR transduced γδ-T cells

Project description:RNA expression of unstimulated γδ-T cells,γδ-TCR-stimulated γδ-T cells, unstimulated αβ-TCR transduced γδ-T cells and αβ-TCR-stimulated αβ-TCR transduced γδ-T cells.

2023-09-07 | GSE216880 | GEO

SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire

Project description:SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire

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Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-12-31 | GSE224721 | GEO

γδ-T cells and αβ-TCR transduced γδ-T cells

Project description:γδ-T cells and αβ-TCR transduced γδ-T cells

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TCR repertoire analysis revealed the highly conserved TCR repertoire in the bilateral tumor in mice

Project description:Temporal analysis of T-cell receptor (TCR) repertoire has been used to monitor treatment-induced changes in antigen-specific T cells in patients with cancer. However, lack of experimental model that allows the temporal analysis of TCR repertoire in same individual in homogeneous population limit the understanding of causal relationship between changes in TCR repertoire and antitumor responses. A bilateral tumor model, in which tumor cells were inoculated into the bilateral backs of mice, can be used for temporal analysis in TCR repertoire. In this study, we examined the prerequisite for this strategy: TCR repertoire are conserved between the bilateral tumor with same growth rate. The bilateral tumors with equivalent tumor size and draining lymph nodes (dLN) were collected 13 days after the tumor inoculation to analyze the TCR repertoire of CD4+ and CD8+ T cells. Most of the tumor-infiltrating T-cell clones were highly conserved between the bilateral tumors, and the extent of clonal expansion was equivalent. In addition, the similarity between bilateral tumors were equivalent to the heterogeneity in one side of the tumor. The similarity of TCR repertoire in the bilateral dLN was markedly lower than that of the tumor, suggesting that tumor-reactive T-cell clones induced independently in each dLN were integrated during recirculation and then infiltrated the tumor. These findings suggest that our bilateral tumor model is suitable for temporal monitoring of TCR repertoire to evaluate temporal and treatment-induced changes in tumor-reactive T-cell clones.

2021-05-12 | GSE174225 | GEO

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