Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fucosylation of HLA-DRB1 regulates CD4+T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy: CD4+ T Cell Phosphoproteomics

ABSTRACT: Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs)—thus, effective strategies to safely increase itICs are needed. We report that dietary administration of L-fucose induces fucosylation and cell surface enrichment of the MHC-II protein HLA-DRB1 in melanoma cells, triggering CD4+T cell-mediated increases in ItICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance and anti-PD1 responder status in patient melanoma specimens, suggesting the potential use of melanoma fucosylation as a strategy for stratifying patients for immunotherapies. Our findings demonstrate that fucosylation is a key mediator of anti-tumor immunity, and importantly, suggest that L-fucose is a powerful agent for safely increasing ItICs and immunotherapy efficacy in melanoma.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell

DISEASE(S): Melanoma

SUBMITTER: John Koomen

LAB HEAD: Eric Lau, PhD

PROVIDER: PXD038065 | Pride | 2022-12-16

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Activate_DMSO_rep1.raw	Raw
	Activate_DMSO_rep1.raw__F003542_.dta	Raw
	Activate_DMSO_rep1.raw__F003542_.mzid.gz	Mzid
	Activate_DMSO_rep1.raw__F003542_.mzid_Activate_DMSO_rep1.raw__F003542_.MGF	Mzid
	Activate_DMSO_rep2.raw	Raw

Items per page:

1 - 5 of 31

Similar Datasets

Fucosylation of HLA-DRB1 regulates CD4+T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy: HLA-DRB1 Interactomes

Project description:Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs)—thus, effective strategies to safely increase itICs are needed. We report that dietary administration of L-fucose induces fucosylation and cell surface enrichment of the MHC-II protein HLA-DRB1 in melanoma cells, triggering CD4+T cell-mediated increases in ItICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance and anti-PD1 responder status in patient melanoma specimens, suggesting the potential use of melanoma fucosylation as a strategy for stratifying patients for immunotherapies. Our findings demonstrate that fucosylation is a key mediator of anti-tumor immunity, and importantly, suggest that L-fucose is a powerful agent for safely increasing ItICs and immunotherapy efficacy in melanoma.

2022-12-16 | PXD038068 | Pride

Fucosylation of HLA-DRB1 regulates CD4+T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy: Fucoproteomic profiling of CD4 T cells

2022-12-16 | PXD038636 | Pride

Fucosylation of HLA-DRB1 regulates CD4+T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy: Fucose Click Chemistry

2022-12-16 | PXD038303 | Pride

Gene expression profiling of fucose-deficient Fx-/- mice cDC1-enriched splenocytes

Project description:Analysis of the top differentially regulated genes in cDC1 in response to fucose treatment revealed genes enriched in pathways such as immune-effector processes, myeloid leukocyte activation, exocytosis, and secretion. We used microarrays to detail the global programme of gene expression underlying fucosylation deficiency in mouse cDC1 cells

2021-03-10 | GSE163958 | GEO

Gene expression profiling of FUT8 knockdown CL1-5 cells

Project description:Overexpression of fucosyltransferase 8 (FUT8) is found in many cancers including liver, ovarian, thyroid, colorectal and non-small cell lung cancers. Unlike other FUTs which are functionally redundant, FUT8 is the only enzyme responsible for the alpha1,6-linked fucosylation (core fucosylation) by adding fucose to the innermost GlcNAc residue of an N-linked glycan. A growing body of evidence indicates that core fucosylation is important for regulating protein functions, such as EGFR, TGF beta receptor and integrins. To understand the downstream molecular events in response to the global alteration of core fucosylation during cancer progression, microarray analysis was employed to profile the changes in gene expression following FUT8 silencing. The genes significantly (2-fold, P<0.01) changed in CL1-5/shFUT8 cells were selected for functional annotations using a Gene Ontology database. The result revealed that many genes involved in cell adhesion, motility, growth, angiogenesis, and inflammation were under the control of core fucosylation.

2012-12-07 | GSE42405 | GEO

The functional role of L-fucose on dendritic cell function and polarization

Project description:Despite significant advances in the development and refinement of immunotherapies administered to combat cancer over the past decades, a number of barriers continue to limit their efficacy. One significant clinical barrier is the inability to mount initial immune responses towards the tumor. As dendritic cells are central initiators of immune responses in the body, the elucidation of mechanisms that can be therapeutically leveraged to enhance their functions to drive anti-tumor immune responses is urgently needed. Here, we report that the dietary sugar L-fucose can be used to enhance the immunostimulatory activity of dendritic cells (DCs). L-fucose polarizes immature myeloid cells towards specific DC subsets, specifically cDC1 and moDC subsets. In vitro, L-fucose treatment enhances antigen uptake and processing of DCs. Furthermore, our data suggests that L-fucose-treated DCs increase stimulation of T cell populations. Consistent with our functional assays, single-cell RNA sequencing of intratumoral DCs from tumor-bearing mice confirmed transcriptional regulation and antigen processing as pathways that are significantly altered by dietary L-fucose. Together, this study provides the first evidence of the ability of L-fucose to bolster DC functionality and provides rational to further investigate how L-fucose can be used to leverage DC function in order to enhance current immunotherapy.

2024-03-20 | GSE261971 | GEO

The Functional Role of L-fucose on Dendritic Cell Function and Polarization

Project description:Despite significant advances in the development and refinement of immunotherapies administered to combat cancer over the past decades, a number of barriers continue to limit their efficacy. One significant clinical barrier is the inability to mount initial immune responses towards the tumor. As dendritic cells are central initiators of immune responses in the body, the elucidation of mechanisms that can be therapeutically leveraged to enhance their functions to drive anti-tumor immune responses is urgently needed. Here, we report that the dietary sugar L-fucose can be used to enhance the immunostimulatory activity of dendritic cells (DCs). L-fucose polarizes immature myeloid cells towards specific DC subsets, specifically cDC1 and moDC subsets. In vitro, L-fucose treatment enhances antigen uptake and processing of DCs. Furthermore, our data suggests that L-fucose-treated DCs increase stimulation of T cell populations. Consistent with our functional assays, single-cell RNA sequencing of intratumoral DCs from breast tumor-bearing mice confirmed transcriptional regulation and antigen processing as pathways that are significantly altered by dietary L-fucose. Together, this study provides the first evidence of the ability of L-fucose to bolster DC functionality and provides rational to further investigate how L-fucose can be used to leverage DC function in order to enhance current immunotherapy.

2024-03-15 | GSE261035 | GEO

Gene expression profiling of FUT8 knockdown CL1-5 cells

2012-12-07 | E-GEOD-42405 | biostudies-arrayexpress

Aberrant L-Fucose accumulation and increased core fucosylation are specific metabolic liabilities in mesenchymal glioblastoma

Project description:Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs). Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker. Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.

2022-11-08 | GSE202200 | GEO

Accelerating Sample Preparation for Proteomics of Formalin Fixed Paraffin Embedded Tumor Tissues to Enable Biomarker Analysis

Project description:Archived tumor specimens are routinely preserved by formalin fixation and paraffin embedding. Despite the conventional wisdom that proteomics might be ineffective due to the crosslinking and pre-analytical variables, these samples have been demonstrated to be useful for both discovery and targeted proteomics. Building on this capability, proteomics approaches can be used to maximize our understanding of cancer biology and clinical relevance by studying preserved tumor tissues annotated with the patients’ medical histories. Proteomics of formalin fixed paraffin embedded (FFPE) tissues also integrates with histological and molecular pathology strategies, so that additional biopsies or resected tumor aliquots do not need to be used. The acquisition of data from the same tumor sample also overcomes concerns about biological variation between samples due to intratumoral heterogeneity. However, the sample preparation for FFPE can be onerous, particularly for very precious (i.e., limited) samples. Therefore, we compared a modified version of the well-established filter-aided sample preparation strategy to a recently introduced kit-based EasyPep method using laser capture microdissected lung adenocarcinoma tissues from a genetically engineered mouse model. This model system allows control over the tumor preparation and pre-analytical variables, while also enabling the development of methods for spatial proteomics to examine intratumoral heterogeneity.

2023-11-28 | PXD045879 | Pride

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