Similar Datasets
Project description:Single-cell RNA-sequencing of γδ-T cells from peripheral blood and breast tumour microenvironment.
| PRJNA594341 | ENA
Project description:Triple negative breast cancer (TNBC) lacks targeted therapy options. TNBC is enriched in breast cancer stem cells (BCSCs), which play a key role in metastasis, chemoresistance, relapse and mortality. γδ T cells hold great potential in immunotherapy against cancer, and might be an alternative to target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor sensing, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. We show that patient derived triple negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T cell immunotherapy. Mechanistically, we unraveled concerted differentiation and immune escape: xenografted BCSCs lost stemness, expression of γδ T cell ligands, adhesion molecules and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither pro-migratory engineered γδ T cells, nor anti-PD 1 checkpoint blockade significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells, and could be pharmacologically reverted by Zoledronate or IFN-α treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.
2023-07-20 | PXD039463 | Pride
Project description:Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here we found that γδ T cell subsets making either IFN-γ or IL-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during γδ thymic development, and were stably maintained in the periphery and within tumours.
2020-09-28 | GSE150585 | GEO
Project description:This clinical trial is an open-label, single-centre, dose escalation, phase I study designed to investigate the safety and tolerability of Haploidentical / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted Gamma Delta (γδ) T Cells (CTM-N2D) in Subjects with Relapsed or Refractory Solid Tumour. The study objectives of this phase I study are to determine the safety, activity and the safe dose of haploidentical or allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells given four times weekly in patients with relapsed or refractory solid tumors of different types.
| 2317628 | ecrin-mdr-crc
Project description:The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. In this study, we used microarrays to uncover the transcriptional responses that occur in small intestinal γδ intraepithelial lymphocytes following bacterial challenge. γδ intraepithelial lymphocytes (γδ IEL) were isolated by flow cytometry from the small intestines of germ-free mice, or from age- and sex-matched conventionally-raised counterparts. We extracted RNAs from these purified γδ IEL for analysis on Affymetrix DNA microarrays. The mice were all >8 weeks in age, and each sample represents a pool of RNAs from 5-8 mice.
2011-04-06 | E-GEOD-28437 | biostudies-arrayexpress
Project description:γδ T cells maintain intestinal immune homeostasis, but their contributions to human ulcerative colitis (UC) are poorly understood. We characterized γδ T cells in intestinal biopsies obtained from patients with UC and healthy donors using single-cell RNA sequencing, T cell receptor profiling, and mass cytometry. UC reduced CD103+Vγ4Vδ1+ intraepithelial γδ lymphocytes (γδ IELs) and increased γδ T cell subsets with stem-like phenotypes expressing T cell factor-1 (TCF-1) and programmed cell death receptor 1 (PD-1), or effector-like phenotypes expressing granzyme B, perforin, and T-box expressed in T cells (T-bet). γδ T cell composition changes in UC correlated with decreased expression of epithelial BTNL3 and BTNL8 and increased BTN3A1 and BTN3A3 , suggesting altered recruitment and activation . Clinical improvement recovered γδ IELs and reduced inflammation-associated subsets. Inflammation-associated changes were observed in peripheral blood γδ T cells. Thus, distinct γδ T cell subsets in different niches exert protective or pathogenic functions in UC.
2026-01-13 | GSE316069 | GEO
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
Project description:γδ-T lymphocytes are cells of the innate immune system exerting potent natural cytotoxicity against bacteria, viruses and tumours. This ability, coupled with their negligible alloreactivity, makes them attractive for adoptive immunotherapy approaches. To achieve a cell product suitable for clinical use, a protocol offering the possibility to generate and expand high numbers of polyclonal γδ-T cells is required. In this study, we designed a robust protocol to either manually or automatically expand high numbers of functional polyclonal memory γδ-T cells under good manufacturing practice conditions, with the additional possibility of gene-modification to improve anti-tumour activity, proving the feasibility of establishing an allogeneic “third-party T-cell bank” for off-the-shelf use. Engineered artificial antigen-presenting cells (aAPCs) expressing CD86/41BBL/CD40L and the cytomegalovirus (CMV)-antigen-pp65 were used for γδ-T cell production. The presence of CMV-pp65 and CD40L proved to be crucial for expansion of the memory Vδ1 subpopulation. To allow clinical translation and guarantee patient safety, aAPCs were stably transduced with an inducible suicide gene. The proposed cell product represents an attractive therapeutic option endowed with broad clinical applications, including treatment of viral infections in highly immunocompromised patients, treatment of aggressive malignancies refractory to conventional approaches and, ultimately, innovative platform for development of off-the-shelf CAR-T-cell products.
2019-11-18 | PXD015506 | Pride
Project description:Background: Peripheral blood mononuclear cells (PBMCs) are relatively easily obtainable cells in humans. Gene expression profiles of PBMCs have been shown to reflect the pathological and physiological state of a person. Recently, we showed that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) has a functional role in human PBMCs during fasting. However, the extent of the role of PPARα in human PBMCs remains unclear. In this study, we therefore performed gene expression profiling of PBMCs incubated with the specific PPARα ligand WY14,643. Results: Incubation of PBMCs with WY14,643 for 12 hours resulted in a differential expression of 1,373 of the 13,080 genes expressed in the PBMCs. Gene expression profiles showed a clear individual response to PPARα activation between six healthy human blood donors, which was not the result of the nutritional status of the donors. Pathway analysis showed that genes in fatty acid metabolism, primarily in β-oxidation were up-regulated upon activation of PPARα with WY14,643, and genes in several amino acid metabolism pathways were down-regulated. Conclusions: This study shows that PPARα in human PBMCs regulates fatty acid and amino acid metabolism. In addition, PBMC gene expression profiles show individual responses to WY14,643 activation. We show that PBMCs are a suitable model to study changes in PPARα activation in healthy humans. Keywords: metabolic state analysis
2008-06-06 | GSE11289 | GEO
Project description:Monocytes from peripheral blood of tumour-bearing (B6Tg(MMTV-PyMT)634Mul/Lellj) or non-tumor-bearing C57BL/6JCrl mice were FACS sorted and single cells analysed by SMARTseq2
2023-06-30 | GSE183838 | GEO