Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell transcriptomic sequencing identifies the genes related to polyfunctionality of persistent CAR-T cells targeting B7-H3 (CD276) in mice bearing human neuroblastoma xenografts

ABSTRACT: To understand the molecular determinants of B12(VHH)-CAR-T polyfunctionality, we simultaneously measured the protein and RNA expression levels of 95 single CD4+ B12(VHH)-CAR-T cells isolated from IMR5 tumor-bearing mouse and re-stimulated with IMR5 tumor cells in vitro. We identified two CAR-T clusters, low polyfunctionality and high polyfunctionality subsets, in a 2D t-SNE plot. Moreover, our single-cell mRNA expression profiling revealed 32 genes that displayed statistically significant, concordant differences between the two cell subsets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221411 | GEO | 2023/08/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

A single-cell proteomic and transcriptomic assay identifies genes related to polyfunctionality of CAR-T cells targeting GPC1 in pancreatic cancer

Project description:To understand the molecular determinants of CAR-T cell polyfunctionality, we simultaneously measured the protein and RNA expression levels of 23 single CD8+ D4-IgG4H-CD28TM CAR T cells targeting GPC1 stimulated with T3M4 pancreatic cancer cells. We identified two CAR-T clusters, low polyfunctionality and high polyfunctionality subsets, in a 2D t-SNE plot. Moreover, our single-cell mRNA expression profiling revealed 23 genes that displayed statistically significant, concordant differences between the two cell subsets.

2023-03-04 | GSE220536 | GEO

B7-H3/CD276: An Emerging Cancer Immunotherapy.

Project description:Immunotherapy aiming at suppressing tumor development by relying on modifying or strengthening the immune system prevails among cancer treatments and points out a new direction for cancer therapy. B7 homolog 3 protein (B7-H3, also known as CD276), a newly identified immunoregulatory protein member of the B7 family, is an attractive and promising target for cancer immunotherapy because it is overexpressed in tumor tissues while showing limited expression in normal tissues and participating in tumor microenvironment (TME) shaping and development. Thus far, numerous B7-H3-based immunotherapy strategies have demonstrated potent antitumor activity and acceptable safety profiles in preclinical models. Herein, we present the expression and biological function of B7-H3 in distinct cancer and normal cells, as well as B7-H3-mediated signal pathways in cancer cells and B7-H3-based tumor immunotherapy strategies. This review provides a comprehensive overview that encompasses B7-H3's role in TME to its potential as a target in cancer immunotherapy.

| S-EPMC8326801 | biostudies-literature

Single-cell transcriptomic sequencing identifies the genes related to polyfunctionality of persistent CAR-T cells targeting B7-H3 (CD276) in mice bearing human neuroblastoma xenografts

Project description:Single-cell transcriptomic sequencing identifies the genes related to polyfunctionality of persistent CAR-T cells targeting B7-H3 (CD276) in mice bearing human neuroblastoma xenografts

| PRJNA914262 | ENA

NRF2 is a spatiotemporal metabolic hub driving the polyfunctionality of Th2 cells in allergic asthma

Project description:Polyfunctional T cell responses are detrimental in immune disorders; however, it is unclear how effector T cell subsets acquire polyfunctionality in tissues. Here, we demonstrate that the activation of Nrf2 is necessary for the differentiation polyfunctional Th2 cells in vivo. Reactive oxygen species (ROS) levels are significantly elevated in lung-infiltrating immune cells during allergic asthma, and inhibiting either ROS or Nrf2 significantly decreases eosinophilia and polyfunctional Th2 cells in the lung. In vivo studies using multiple cell-type specific Nrf2-deficient mice and mixed bone marrow chimeras revealed that cell-intrinsic Nrf2 drives IL-5 and IL-13 expression in Th2 cells independently of IL-33. Mechanistically, Nrf2 promotes optimal OXPHOS and glycolysis capacity by inducing PPARg expression and glucose uptake to drive polyfunctionality of Th2 cells. Blocking Nrf2 reduces IL-5 and IL-13 production from house dust mite allergen-specific Th2 cells obtained from asthma patients. These findings demonstrate that Nrf2 acts as a spatiotemporal metabolic hub driving the differentiation of polyfunctional Th2 cells, which may have therapeutic implications for controlling allergic lung inflammation.

2023-08-24 | GSE241138 | GEO

Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer.

Project description:B7-H3 (CD276), a member of the family of immune modulators, orchestrates antitumor immunity. To date, only small-sized studies have examined the association of B7-H3 expression with survival in pancreatic cancer, yielding inconclusive results. We evaluated tumor B7-H3 expression in 150 consecutive patients with pancreatic ductal adenocarcinoma using immunohistochemistry. B7-H3 expression was positive (≥10% tumor cells) in 99 of 150 (66%) cases of pancreatic cancer. We classified the tumors into four groups depending on B7-H3 expression (negative, low, intermediate, and high) and found that higher B7-H3 expression was independently associated with lower disease-free survival (DFS; for high vs. negative B7-H3 expression: multivariable hazard ratio (HR) = 3.12; 95% confidence interval (CI) = 1.48?6.15; Ptrend = 0.0026). Furthermore, the association of B7-H3 expression with survival differed according to the pathological stage (p-stage) (Pinteraction = 0.048, between p-stages I?II and III?IV). The association of B7-H3 positivity with lower DFS was stronger in tumors with p-stage I?II (multivariable HR = 3.10, 95% CI = 1.75?5.69; P < 0.0001) than in those with p-stage III?IV (multivariable HR = 1.20, 95% CI = 0.67?2.28; P = 0.55). We demonstrated that tumor high B7-H3 expression is independently associated with poor survival in patients with pancreatic cancer and that this association is stronger in tumors with p-stage I?II than in those with p-stage III?IV. B7-H3 expression may be a useful prognostic biomarker for identifying aggressive early-stage pancreatic cancer.

| S-EPMC6069252 | biostudies-literature

Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy.

Project description:B7-H3 (CD276) is an important immune checkpoint member of the B7 and CD28 families. Induced on antigen-presenting cells, B7-H3 plays an important role in the inhibition of T-cell function. Importantly, B7-H3 is highly overexpressed on a wide range of human solid cancers and often correlates with both negative prognosis and poor clinical outcome in patients. Challenges remain to identify the receptor(s) of B7-H3 and thus better elucidate the role of the B7-H3 pathway in immune responses and tumor evasion. With a preferential expression on tumor cells, B7-H3 is an attractive target for cancer immunotherapy. Based on the clinical success of inhibitory immune checkpoint blockade (CTLA-4, PD-1, and PD-L1), mAbs against B7-H3 appear to be a promising therapeutic strategy worthy of development. An unconventional mAb against B7-H3 with antibody-dependent cell-mediated cytotoxicity is currently being evaluated in a phase I clinical trial and has shown encouraging preliminary results. Additional therapeutic approaches in targeting B7-H3, such as blocking mAbs, bispecific mAbs, chimeric antigen receptor T cells, small-molecule inhibitors, and combination therapies, should be evaluated, as these technologies have already shown positive results in various cancer settings. A better understanding of the B7-H3 pathway in humans will surely help to further optimize associated cancer immunotherapies. Clin Cancer Res; 22(14); 3425-31. ©2016 AACR.

| S-EPMC4947428 | biostudies-literature

Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma.

Project description:BackgroundAdrenocortical carcinoma (ACC) is a rare malignant endocrine tumor with a high tumor recurrence rate and poor postoperative survival. Recent studies suggest that CD276- (B7-H3) targeted therapy represents a promising therapeutic option for solid tumors. However, little is known about the expression status of CD276 or its association with progression and prognosis of ACC.MethodsClinical data were retrospectively analyzed from patients who underwent resection of ACC at our institution (n = 48). Archived, formalin-fixed, and paraffin-embedded samples were collected for immunohistochemical analysis, and the correlation between CD276 expression and clinicopathological parameters was evaluated. Kaplan-Meier and univariate/multivariate Cox regression methods were implemented to identify any prognostic effects. Data from The Cancer Genome Atlas (TCGA) ACC cohort (n = 48). Archived, formalin-fixed, and paraffin-embedded samples were collected for immunohistochemical analysis, and the correlation between CD276 expression and clinicopathological parameters was evaluated. Kaplan-Meier and univariate/multivariate Cox regression methods were implemented to identify any prognostic effects. Data from The Cancer Genome Atlas (TCGA) ACC cohort (.ResultsPositive expression of CD276 was detected on the cell membrane and in the cytoplasm of cancer cells or tumor-associated vascular cells in 91.67% (44/48) of ACCs. Vascular expression of CD276 was associated with local aggression (higher T stage, P = 0.029) and advanced ENSAT stage (P = 0.029) and advanced ENSAT stage (P = 0.029) and advanced ENSAT stage (P = 0.029) and advanced ENSAT stage (P = 0.029) and advanced ENSAT stage (P = 0.029) and advanced ENSAT stage (.ConclusionThese findings highlight the immune checkpoint factor CD276 as an independent prognostic factor and a potential therapeutic target in ACC.

| S-EPMC6977319 | biostudies-literature

RNA sequencing comparison of B7-H3.TMIGD2 and B7-H3.CD28.4-1BB CAR-T cells in vitro

Project description:CAR-T cell costimualtory domains can alter CAR-T cell phenotypes. We therefore performed RNA sequencing to understand the effect of TMIGD2 vs CD28.4-1BB comstimulation in B7-H3 CAR-T cells after in vitro coculture.

2024-05-08 | GSE254544 | GEO

Overexpression of FOXO1 enhances CAR T cell polyfunctionality, metabolic fitness and efficacy against solid tumors

Project description:Overexpression of FOXO1 enhances CAR T cell polyfunctionality, metabolic fitness and efficacy against solid tumors

| PRJNA936106 | ENA

The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development.

Project description:The immune checkpoint B7-H3 (CD276) is a member of the B7 family that has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. Here, we show that B7-H3 is highly expressed in mouse and human adipose tissue at steady state, with the highest levels in adipocyte progenitor cells. B7-H3 is rapidly down-regulated upon the initiation of adipocyte differentiation. Combined RNA sequencing and metabolic studies reveal that B7-H3 stimulates glycolytic and mitochondrial activity of adipocyte progenitors. Loss of B7-H3 in progenitors results in impaired oxidative metabolism program and increased lipid accumulation in derived adipocytes. Consistent with these observations, mice knocked out for B7-H3 develop spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation. Our results reveal an unexpected metabolic role for B7-H3 in adipose tissue and open potential new avenues for the treatment of metabolic diseases by targeting the B7-H3 pathway.

| S-EPMC9045715 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data