Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PD-L1 ubiquitination by MIB2 enables its translocation to the plasma membrane for tumor immune evasion

ABSTRACT: PD-L1 ubiquitination by MIB2 enables its translocation to the plasma membrane for tumor immune evasion

PROVIDER: PRJNA906110 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22430454.fastq.gz	Fastqsanger.gz
	SRR22430455.fastq.gz	Fastqsanger.gz
	SRR22430456.fastq.gz	Fastqsanger.gz

Items per page:

1 - 3 of 3

Similar Datasets

PD-L1 ubiquitination by MIB2 enables its translocation to the plasma membrane for tumor immune evasion

Project description:Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is a transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to the plasma membrane to interact with programmed death 1 (PD-1) expressed on T cell surface. This interaction delivers co-inhibitory signals to T cells, thereby suppressing their function and evading antitumor immunity. Most companion or complementary diagnostic devices for PD-L1 expression levels in tumor cells used in the clinic or clinical trials require membranous staining. However, the mechanism driving PD-L1 translocation to the plasma membrane after de novo synthesis is poorly understood. Herein, we showed that mind bomb homolog 2 (MIB2) is required for PD-L1 transportation from the trans-Golgi network (TGN) to the plasma membrane of cancer cells. MIB2 deficiency leaded to fewer PD-L1 proteins on the tumor cell surface and promotes antitumor immunity in mice.We performed a single-cell RNA sequencing (scRNA-seq) of B16-F10 tumors from C57BL/6 syngeneic mice. Knockdown of MIB2 resulted in an increase in the percentage of CD8+ CTLs (approximately 5-fold) and CD4+/CD8+ effector/activated T cells (approximately 2-fold), indicating that MIB2 downregulation enhanced the antitumor immune activity centered on CD8+ CTLs and changed their transcriptional profile. Our findings demonstrate that non-proteolytic ubiquitination of PD-L1 by MIB2 is required for its transportation to the plasma membrane and tumor cells' immune evasion.

2023-12-31 | GSE218906 | GEO

PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination.

Project description: Not available

| S-EPMC9888393 | biostudies-literature

A tumor specific super-enhancer drives immune evasion by guiding synchronous expression of PD-L1 and PD-L2

Project description:A tumor specific super-enhancer drives immune evasion by guiding synchronous expression of PD-L1 and PD-L2

2019-07-30 | GSE135016 | GEO

SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion

Project description:Although genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection, cancer cells often evade these responses by overexpressing immune checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 as a factor that favors tumor immune evasion by a dual mechanism involving both the suppression of innate immune signaling and the induction of PD-L1-mediated immune checkpoint responses. Mechanistically, SMARCAL1 relieves endogenous DNA damage and suppresses cGAS-STING-dependent immune signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a transcriptional regulatory element in the PD-L1 gene, thereby promoting PD-L1 expression in cancer cells. Loss of SMARCAL1 enhances anti-tumor immune responses and sensitizes tumors to immune checkpoint blockade in a mouse melanoma model. Collectively, these studies uncover SMARCAL1 as a valuable target for cancer immunotherapy.

2024-01-24 | PXD046384 | Pride

SMARCD1 is a dual regulator of PD-L1 expression and cell proliferation facilitating tumor evasion

Project description:Cancer cells often evade immune responses by overexpressing immune checkpoint regulators, such as PD-L1. Here we identify a subunit of mating-type switching /sucrose fermentation (SWI/SNF) complex as a factor that favors tumor evasion by a dual mechanism involving both the induction of PD-L1-mediated immune checkpoint responses and the tumor cell proliferation. SMARCD1 deficient cancer cells exhibit not only reduced PD-L1 expression in vitro but also significantly suppressed tumor growth. Mechanistically, SMARCD1 maintains chromatin accessibility at PD-L1 transcriptional regulatory element thereby promoting PD-L1 expression in cancer cells. Besides, SMARCD1 might promote cancer cell proliferation by effecting several pathways such as AI3K-Akt signaling pathways. Collectively, these studies uncover SMARCD1 as a promising target for colorectal cancer (CRC) treatment.

2025-04-22 | GSE275535 | GEO

ID3 Enhances PD-L1 Expression by Restructuring MYC and Promotes Colorectal Cancer Immune Evasion [ChIP-seq]

Project description:The inhibitor of DNA-binding protein ID3 is a vital component of immune cells and has been associated with the progression of colorectal cancer (CRC). Despite its significance, its specific role in the immune evasion strategies utilized by CRC remains unclear. RNA-seq analysis revealed that ID3 is associated with the PD-L1 immune checkpoint. We further demonstrated that ID3 modulates PD-L1 expression, suppresses the infiltration and activation of CD8+ T cells, and facilitates the immune escape of CRC cells. Additionally, we found that the knockdown of ID3 significantly enhanced the effectiveness of PD-L1 antibody treatment in combating CRC, reduced the upregulation of PD-L1 induced by the antibody, and altered the immune microenvironment within CRC. Mechanistically, our biological and structural analyses demonstrated that ID3 reconstructed the four-dimensional structure of MYC, thereby enhancing its binding affinity to the PD-L1 promoter and augmenting PD-L1 transcriptional activity. By integrating analysis of ChIP-seq, RNA-seq, and ImmPort gene sets, we found that ID3's DNA-assisted binding function was widespread and could either enhance or suppress gene transcription, not only affecting tumor immune escape through immune checkpoints, but also regulating various cytokines and immune cells involved in tumor immunity. In conclusion, our study uncovered a new mechanism by which ID3 promotes immune evasion in CRC and targeting ID3 may improve the efficacy of anti-PD-1/PD-L1 immunotherapy.

2024-09-30 | GSE275455 | GEO

ID3 Enhances PD-L1 Expression by Restructuring MYC and Promotes Colorectal Cancer Immune Evasion [RNA-seq]

2024-09-30 | GSE275454 | GEO

CDK5-dependent phosphorylation and nuclear translocation of TRIM59 promotes macroH2A1 ubiquitination and tumorigenicity

Project description:CDK5-dependent phosphorylation and nuclear translocation of TRIM59 promotes macroH2A1 ubiquitination and tumorigenicity

| PRJNA542104 | ENA

DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion [CRISPR screen]

Project description:RNA-binding proteins (RBPs) can recognize thousands of RNAs that help to maintain cell homeostasis, and RBP dysfunction is frequently observed in various cancers. However, whether specific RBPs are involved in tumor immune evasion by regulating programmed death ligand-1 (PD-L1) is unclear. We performed targeted RBP CRISPR/Cas9 screening and identified density regulated re-initiation and release factor (DENR) as a PD-L1 regulator. DENR-depleted cancer cells exhibited reduced PD-L1 expression in vitro and in vivo. DENR depletion significantly suppressed tumor growth and enhanced the tumor-killing activity of CD8+ T cells. Mechanistically, DENR antagonized the translational repression of three consecutive upstream open reading frames (uORFs) upstream of Janus kinase 2 (JAK2); thus, DENR deficiency impaired JAK2 translation and the IFNγ-JAK-STAT signaling pathway, resulting in reduced PD-L1 expression in tumors. Overall, we discovered that the RBP DENR is a novel regulator in PD-L1 expression and highlighted the potential of DENR as a therapeutic target for immunotherapy.

2022-02-28 | GSE184048 | GEO

HSV-1 temporally orchestrates RAP80 ubiquitination to balance viral replication and evasion [RNA-seq]

Project description:HSV-1 temporally orchestrates RAP80 ubiquitination to balance viral replication and evasion [RNA-seq]

| PRJNA1440365 | ENA