Expression data from iPSC-derived mimetic Vγ9Vδ2 T cells and mimetic NK cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE126035 | GEO | 2019/05/31
REPOSITORIES: GEO
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Project description:Expression data from iPSC-derived mimetic Vγ9Vδ2 T cells and mimetic NK cells
| PRJNA520837 | ENA
Project description:Objectives: Vγ9Vδ2 T-cells are a subset of T-cells with a crucial role in immunosurveillance which can be activated and expanded by multiple means to stimulate effector responses. Little is known about the expression of checkpoint molecules on this cell population and whether the ligation of these molecules can regulate their activity. The aim of this study was to assess the expression of both activatory and inhibitory receptors on Vγ9Vδ2 T-cells to assess potential avenues of regulation to target with immunotherapy. Methods: Expression of various activatory and inhibitory receptors was assessed on Vγ9Vδ2 T-cells by flow cytometry following activation and expansion using zoledronic acid (ZA) and Bacillus Calmette-Guérin (BCG). Expression of these markers and production of effector molecules was also examined following co-culture with various tumour cell targets. The effect of immune checkpoint blockade on Vγ9Vδ2 T-cells was also explored. Results: Vγ9Vδ2 T-cells expressed high levels of activatory markers both at baseline and following stimulation. Vγ9Vδ2 T-cells expressed variable levels of inhibitory checkpoint receptors with many being upregulated following stimulation. Expression of these markers is further modulated upon co- culture with tumour cells with changes reflecting activation and effector functions. Despite their high expression of inhibitory receptors when cultured with tumour cells expressing cognate ligands there was no effect on Vδ2+ T-cell cytotoxic capacity or cytokine production with immune checkpoint blockade. Conclusions: Our work suggests the expression of checkpoint receptors present on Vγ9Vδ2 T-cells which may provide a mechanism with the potential to be utilised by tumour cells to subvert Vγ9Vδ2 T-cell cytotoxicity. This work suggests important candidates for blockade by ICI therapy in order to increase the successful use of Vγ9Vδ2 T-cells in immunotherapy.
2023-01-02 | GSE221563 | GEO
Project description:Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14+ cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.
2022-11-09 | GSE173387 | GEO
Project description:To better understand the mechanisms underlying the different antitumor activity of Vγ9Vδ2-T cells induced by PA or OA, we performed the proteomic analysis of Vγ9Vδ2-T cells cultured under different conditions.
2025-07-14 | PXD064016 | Pride
Project description:Recent advancements in cancer immunotherapies have highlighted the potential of Vγ9Vδ2 T cells as key players in the immune response against cancer. These cells, initially recognized for their broad activity in combating infections and tumors, are now emerging as promising candidates for targeted immunotherapeutic strategies, including T cell Engagers (TCEs). However, like other immune cells, Vγ9Vδ2 T cells can enter a state of dysfunction and exhaustion within the tumor microenvironment, driven by factors such as TCR overstimulation, immunosuppressive cytokines (e.g., TGF-β), and hypoxia. While the mechanisms of T cell exhaustion have been extensively studied in in vivo CD8+ T cells, the lack of a murine Vγ9Vδ2 subset complicates the investigation and generation of large numbers of exhausted Vγ9Vδ2 T cells. To address this, we present a novel in vitro protocol for rapidly generating exhausted Vγ9Vδ2 T cells through co-culture with Zoledronate activated human tumor cells. We characterized the resulting cells using phenotypic, metabolomic, and transcriptomic analyses, comparing their profiles to published data on in vivo-exhausted cells. Furthermore, we measured the reactivation potential of these exhausted Vγ9Vδ2 T cells using anti-CD3 monoclonal antibodies, demonstrating that CD3 stimulation can partially reverse exhaustion and restore anti-tumor effector functions. Furthermore, exhausted Vγ9Vδ2 T cells retained some cytotoxic activity upon stimulation with T Cell Engagers, underscoring the versatility and applicability of our in vitro exhaustion model. This model offers a robust platform for the evaluation of novel immunotherapies targeting Vγ9Vδ2 T cells, facilitating preclinical assessments before transitioning to in vivo studies.
2026-07-31 | GSE303586 | GEO
Project description:Although tear replacement and anti-inflammatory treatments have been thoroughly investigated, a method to induce epithelial restoration is lacking. Here, we asked whether WNT signaling activation via an antibody-based WNT mimetic platform might activate lacrimal gland acinar cells and restore tear secretion. Transcriptional and cellular changes were investigated using single cell sequencing. In a mouse model of dry eye disease, and intra-lacrimal gland treatment with a WNT mimetic targeting FZD1, 2, and 7 reversed aqueous tear deficiency. After excretory duct ligation damage, WNT mimetic treatment promoted acinar cell restoration and increased detectable tear volume production. We demonstrate a role for WNT signaling in acinar cell proliferation, and scRNA-seq revealed that the WNT mimetic promotes pathway activation and proliferation in injury-induced states. Our findings extend the potential for WNT pathway activation via a ligand mimetic platform to lacrimal gland regeneration.
2025-06-10 | GSE295860 | GEO
Project description:Releasing the restraints of Vγ9Vδ2 T-cells in cancer immunotherapy
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Project description:We studied whether Vγ9Vδ2-T cells can exploited as autologous effector lymphocytes in chronic lymphocytic leukemia (CLL). Healthy controls (HC) Vγ9Vδ2-T cells were activated by and had potent cytolytic activity against CLL cells, however CLL-derived Vγ9Vδ2-T cells proved dysfunctional with respect to effector cytokine production and cytotxicity. Dysfunction of Vγ9Vδ2-T cells was reversible upon activation with autologous monocyte-derived dendritic cells (mODCs). RNA sequencing confirmed that Vγ9Vδ2-T cells from CLL patients have a transcriptional profile that is distinct from HC Vγ9Vδ2-T cells prior to ex vivo expansion, although the profile after ex vivo expansion is similar between CLL and HC Vγ9Vδ2-T cells. Gene expression profiling implicated alterations in both synapse formation and exhaustion as conceivable contributors to compromised Vγ9Vδ2-T cell function in CLL patients. Taken together, CLL-mediated dysfunction of autologous Vγ9Vδ2-T cells is fully reversible, resulting in potent cytotoxicity towards CLL cells.
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