Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mannose enhances anti-PD-1 therapy efficacy in ovarian cancer via modulating gut microbial metabolite [CD8]

ABSTRACT: The gut microbiome plays a critical role in enhancing the effectiveness of immune checkpoint blockade (ICB) therapy. Here, we demonstrate that oral supplementation with the prebiotics mannose slows tumor growth in immunocompetent mice in a manner dependent on the gut microbiota. This effect is associated with an increase in the abundance of Faecalibaculum. Mannose generates an immune-stimulatory tumor microenvironment (TME), characterized by a higher percentage of effector and memory CD8+ T cells, along with a notable immunoreactive gene expression signature. Crucially, mannose modulates the stemness program of CD8+ T cells and promotes the generation of progenitor exhausted CD8+ T cells (Tpex). Mechanistically, mannose enhances the production of the short-chain fatty acids (SCFA) propionate and butyrate by the gut microbiota. Administration of propionate and butyrate suppresses tumor progression and stimulates the expansion and differentiation of Tpex both in vivo and in vitro. Furthermore, mannose works synergistically with PD-1 blockade, resulting in tumor regression and enhanced differentiation of intratumoral Tpex into intermediate exhausted CD8+ T cells (Tex-int) and terminally exhausted CD8+ T cells (Tex-term). We also identified a gene signature related to mannose therapy that correlates with favorable responses to ICB across various cancers. Overall, our findings support the combination of mannose dietary supplementation with anti-PD-1 immunotherapy in treating ovarian cancer and suggest its potential for clinical application.

ORGANISM(S): Mus musculus

PROVIDER: GSE285964 | GEO | 2025/03/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Mannose enhances anti-PD-1 therapy efficacy in ovarian cancer via modulating gut microbial metabolite.

Project description:The gut microbiome serves as a crucial mediator for improving the efficacy of immune checkpoint blockade (ICB) therapy. Here, we show that oral supplementation with prebiotics (mannose) retarded tumor growth in immunocompetent mice in a gut microbiota dependent manner, correlating with the enrichment of Faecalibaculum. Mannose generates an immune-stimulatory tumor microenvironment (TME) characterized by an increase percentage of effector and memory CD8+T cells, accompanied by a prominent immunoreactivegeneexpressionsignature. Most importantly, mannose modulates the stemness program of CD8+T cells and facilitates the generation of progenitor exhausted CD8+T cells (Tpex). Mechanistically, mannose increases gut microbial production of the short-chain fatty acids (SCFA) propionate and butyrate. Administration of propionate and butyrate suppresses tumor progression and stimulates the expansion and differentiation of Tpex both in vivo and in vitro. Mannose synergized with PD-1 blockade in tumor regression and augmented intratumoral Tpex differentiation into intermediate exhausted CD8+T cells (Tex-int) and terminally exhausted CD8+T cells (Tex-term). Moreover, we identified a mannose-therapy related gene signature associated with favorable responses to ICB in pan-cancer. Overall, our findings support the rationale for combining dietary supplementation of mannose with anti-PD-1 immunotherapy in ovarian cancer, and its clinical translation.

2025-03-17 | GSE271477 | GEO

Mannose enhances anti-PD-1 therapy efficacy in ovarian cancer via modulating gut microbial metabolite

Project description:The gut microbiome plays a critical role in enhancing the effectiveness of immune checkpoint blockade (ICB) therapy. Here, we demonstrate that oral supplementation with the prebiotics mannose slows tumor growth in immunocompetent mice in a manner dependent on the gut microbiota. This effect is associated with an increase in the abundance of Faecalibaculum. Mannose generates an immune-stimulatory tumor microenvironment (TME), characterized by a higher percentage of effector and memory CD8+ T cells, along with a notable immunoreactive gene expression signature. Crucially, mannose modulates the stemness program of CD8+ T cells and promotes the generation of progenitor exhausted CD8+ T cells (Tpex). Mechanistically, mannose enhances the production of the short-chain fatty acids (SCFA) propionate and butyrate by the gut microbiota. Administration of propionate and butyrate suppresses tumor progression and stimulates the expansion and differentiation of Tpex both in vivo and in vitro. Furthermore, mannose works synergistically with PD-1 blockade, resulting in tumor regression and enhanced differentiation of intratumoral Tpex into intermediate exhausted CD8+ T cells (Tex-int) and terminally exhausted CD8+ T cells (Tex-term). We also identified a gene signature related to mannose therapy that correlates with favorable responses to ICB across various cancers. Overall, our findings support the combination of mannose dietary supplementation with anti-PD-1 immunotherapy in treating ovarian cancer and suggest its potential for clinical application.

2025-03-17 | GSE285806 | GEO

Mannose enhances anti-PD-1 therapy efficacy in ovarian cancer via modulating gut microbial metabolite [Peritoneum]

2025-03-17 | GSE285965 | GEO

Strength of CD28 costimulation directs self-renewal or differentiation of TCF-1+ PD-1+ CD8 T cells through metabolic regulation

Project description:During persistent antigen stimulation, such as in chronic infections and cancer, T cells differentiate into a hypofunctional exhausted state to survive. Exhausted PD-1+ CD8 T cell responses are sustained by TCF-1+ precursors (Tpex) that self-renew or differentiate into exhausted T cells (Tex) that retain some effector function. Tpex have high expression of the costimulatory molecule CD28 and are the cells that respond to PD-1 targeted immunotherapy. Here, we demonstrate that abrogation of CD28 signaling impairs maintenance of anti-viral T cell responses during chronic infection. Low-level CD28 signaling was required to preserve mitochondrial fitness and self-renewal of Tpex, whereas stronger CD28 signaling enhanced glycolysis and promoted Tpex differentiation. Our findings show that CD28 signaling is essential for long-term maintenance of antigen-specific T cells during chronic stimulation, and suggest that the activation status of antigen presenting cells determines Tpex differentiation into more functional effector-like Tex cells.

2023-07-01 | GSE200506 | GEO

Chronic Type I interferons signaling promotes lipid peroxidation-driven terminal CD8+T cell exhaustion and curtails anti-PD-1 treatment efficacy

Project description:Identifying signals that govern the differentiation of tumor-infiltrating CD8 + T cells (CD8 + TILs) towards exhaustion can improve current therapeutic approaches for cancer. Here, we show that type I interferons (IFN-Is) act as environmental cues enhancing terminal CD8 + T cell exhaustion in tumors. We found enrichment of IFNIs-stimulated genes (ISGs) within exhausted CD8 + T cells (Tex cells) in patients across various cancer types, with heightened ISG levels correlating with poor response to immune checkpoint blockade (ICB) therapy. In preclinical models, CD8 + TILs devoid of IFN-Is signaling developed less exhaustion features, provided better tumor control and showed greater response to ICB-mediated rejuvenation. Mechanistically, chronic IFN-Is stimulation perturbed lipid metabolism and redox balance in Tex cells, leading to aberrant lipid accumulation and elevated oxidative stress. Collectively, these defects promoted lipid peroxidation, which potentiated metabolic and functional exhaustion of Tex cells. Thus, cell intrinsic IFN-Is signaling regulates the extent of CD8+ TIL exhaustion, and has important implications for immunotherapy.

2022-11-16 | GSE212699 | GEO

Chronic Type I interferons signaling promotes lipid peroxidation-driven terminal CD8+T cell exhaustion and curtails anti-PD-1 treatment efficacy [ATAC-Seq]

2022-11-16 | GSE212698 | GEO

Chronic Type I interferons signaling promotes lipid peroxidation-driven terminal CD8+T cell exhaustion and curtails anti-PD-1 treatment efficacy [RNA-Seq]

2022-11-16 | GSE212697 | GEO

NR4A1 transcriptionally regulates the differentiation of stem-like CD8+ T cells in the tumor microenvironment (RNA-Seq)

Project description:CD8+ T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control, and are also the main responders in immunotherapy. Using a new reporter mouse for the orphan nuclear receptor NR4A1, originally characterized critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8+ T cells. Integrating ChIP-seq and RNA-seq analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, and suppresses terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.

2024-05-09 | GSE266287 | GEO

NR4A1 transcriptionally regulates the differentiation of stem-like CD8+ T cells in the tumor microenvironment (ChIP-Seq)

2024-05-09 | GSE266286 | GEO

c-Myb instructs both stemness and functional exhaustion of CD8+ T cells during chronic infection [bulkRNA-seq]

Project description:Chronic viral infections and tumours are associated with CD8+ T cell exhaustion, which is characterized by high expression of inhibitory receptors such as programmed cell death protein 1 (PD-1) and impaired effector function. Understanding the molecular regulation of T cell exhaustion is critical for the development of new immunotherapies. Chronically activated T cells are maintained by precursors of exhausted T (TPEX) cells that express the transcription factor TCF1, self-renew and give rise to TCF-1– exhausted effector T (TEX) cells; this process is currently, however, poorly understood. Here, we reveal that TPEX cells are heterogenous and contain a population of CD62L+ stem-like exhausted T cells that selectively preserve long-term self-renewal capacity and multipotency of antigen-specific T cells during chronic infection. Furthermore, we show that the transcription factor c-Myb is essential for the development of CD62L+ TPEX cells, self-renewal of TPEX cells and the induction of key features of T cell exhaustion. Consequently, Myb-deficient CD8+ T cells show uninhibited cytokine production resulting in fatal immunopathology in response to chronic but not acute LCMV infection and fail to be maintained long-term. Finally, we show that c-Myb-dependent CD62L+ TPEX cells exclusively mediate T cell proliferation during PD-1 checkpoint inhibition and show enhanced antiviral properties, making them attractive targets for new immunotherapeutic strategies. Thus, our findings identify CD62L+ TPEX cells as central to the maintenance of exhausted T cell responses and reveal c-Myb as a key transcriptional orchestrator that combines two central aspects of T cell exhaustion, limitation of T cell function and long-term maintenance during chronic infection.

2022-08-22 | GSE203575 | GEO

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