Similar Datasets
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 | GSE224720 | GEO
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
Project description:Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer
| PRJNA932262 | ENA
Project description:Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [mouse scRNA]
| PRJNA934485 | ENA
Project description:Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [human scRNA]
| PRJNA934486 | ENA
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 immature Gzma + Blk + Etv5 + Tox2 + γδT17 precursor population, and a significant increase in Cd4 + 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.
| S-EPMC10802474 | biostudies-literature
Project description:Objective: To investigate the frequency, phenotype, function, and longitudinal repertoire of mucosal-associated invariant T (MAIT) cells in relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) patients. Methods: Forty-five RRMS patients in remission, 20 RRMS patients experiencing exacerbations, 15 PPMS patients, and 30 healthy controls (HCs) were included in the study. MAIT cells were identified phenotypically as CD3+ TCRγδ- Vα7.2 + CD161high. In 15 patients, MAIT cell number and MRI lesions were evaluated every 6 months, for 36 months. MAIT cell TCRVβ repertoire was defined using single-cell cloning and mRNA sequencing. Results: Circulating MAIT cells were significantly reduced in both RRMS and PPMS patients, particularly during exacerbations, compared to healthy subjects. This decrease was accompanied by pro-inflammatory cytokine production (TNF-α, IFN-γ, IL-17, and GM-CSF). Three months post-exacerbation, peripheral blood MAIT cell percentages increased significantly along with clinical recovery. Likewise, we observed inverse correlation between MRI lesions and peripheral blood MAIT cell numbers. In paired samples, MAIT cell percentage was significantly higher in CSF than in peripheral blood, suggesting MAIT cell migration through the blood-brain barrier. Finally, MAIT cells showed limited TCRVβ repertoires, in both CSF and peripheral blood, which remained stable over time. Conclusions: MAIT cell levels correlated with MS course both clinically and radiologically, showing marked and sustained oligoclonality. These findings may contribute to a better understanding of pathophysiological phenomena underlying the course of MS, and discovery of MAIT cell inhibitors could pave the way for the development of new therapeutic strategies.
| S-EPMC6880779 | biostudies-literature
Project description:γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance.
| S-EPMC5337994 | biostudies-literature
Project description:The mouse thymus produces discrete γδ T cell subsets that make either interferon-γ (IFN-γ) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g(+/-) Cd3d(+/-) (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on γδ T cells. CD3DH mice had normal numbers and phenotypes of αβ thymocyte subsets, but impaired differentiation of fetal Vγ6(+) (but not Vγ4(+)) IL-17-producing γδ T cells and a marked depletion of IFN-γ-producing CD122(+) NK1.1(+) γδ T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-γ(+) γδ T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory γδ T cell subsets and their impact on pathophysiology.
| S-EPMC4875770 | biostudies-literature
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