Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade [scRNA-seq]

ABSTRACT: Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade [scRNA-seq]

PROVIDER: PRJNA903834 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade [scRNA-seq]

Project description:Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse melanoma models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently of tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation in expression, leading to tumor heterogeneity and subclonal resistance.

2023-02-24 | GSE218429 | GEO

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade [scBisulfite-seq]

2023-02-24 | GSE218423 | GEO

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade

Project description:Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade

| PRJNA903816 | ENA

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade [scBisulfite-seq]

Project description:Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade [scBisulfite-seq]

| PRJNA903829 | ENA

Melanoma Sequential Immune Checkpoint Blockade Treatment Sequencing Study

Project description:Melanoma Sequential Immune Checkpoint Blockade Treatment Sequencing Study

| PRJNA397812 | ENA

Molecular patterns of resistance to immune checkpoint blockade in melanoma [NanoString GeoMx]

Project description:Tumor cell-containing Regions of Interest from 17 patients with melanoma after progression to Immune Checkpoint Blockade were profiled at the transcriptomic level.

2024-03-12 | GSE261347 | GEO

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade.

| S-EPMC9981575 | biostudies-literature

Molecular patterns of resistance to immune checkpoint blockade in melanoma

Project description:Molecular patterns of resistance to immune checkpoint blockade in melanoma

| PRJNA1026564 | ENA

Melanoma Sequential Immune Checkpoint Blockade Treatment Sequencing Study

Project description:<p>Blockade of T cell coinhibitory molecules such as CTLA-4 and PD-1, can activate T cell antitumor response. Although these immune checkpoint blockades (CTLA-4 blockade and PD-1 blockade) have shown durable response, response rate is modest. Therefore, there is a need to find stable biomarkers predictive of response to immune checkpoint blockades and to understand underlying resistance mechanisms. We collected longitudinal tumor biopsies from a cohort of metastatic melanoma patients treated with sequential immune checkpoint blockades and performed whole exome sequencing of this cohort. The comprehensive genomic characterization of tumors enabled identification of higher copy number loss burden as a resistance mechanism and clonal T cell repertoire as a predictive biomarker.</p>

| phs001425 | dbGaP

PRMT1 inhibition activates the interferon pathway to potentiate antitumor immunity and enhance checkpoint blockade efficacy in melanoma

Project description:Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyl transferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8+ T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8+T cells in vivo. Moreover, PRMT1 deletion in melanoma cells facilitated formation of double-stranded RNA (dsRNA) derived from endogenous retroviral elements (ERVs) and stimulated an intracellular interferon response. Mechanistically, PRMT1 deficiency repressed the expression of DNA methyltransferase 1 (DNMT1) by attenuating modification of H4R3me2a and H3K27ac at enhancer regions of DNMT1, and DNMT1 downregulation consequently activated ERV transcription and the interferon signaling. Importantly, PRMT1 inhibition with DCPT1061 synergized with PD-1 blockade to suppress tumor progression and increase the proportion of CD8+T cells as well as IFNγ+CD8+T cells in vivo. Together, these results reveal an unrecognized role and mechanism of PRMT1 in regulating antitumor T-cell immunity, suggesting PRMT1 inhibition as a potent strategy to increase the efficacy of ICB.

2023-11-07 | GSE240258 | 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