Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer.

ABSTRACT: Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer.

PROVIDER: PRJNA804401 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR17933300_1.fastq.gz	Fastqsanger.gz
	SRR17933300_2.fastq.gz	Fastqsanger.gz
	SRR17933301_1.fastq.gz	Fastqsanger.gz
	SRR17933301_2.fastq.gz	Fastqsanger.gz
	SRR17933302_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 106

Similar Datasets

Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [CHIP-seq]

Project description:The MYC oncogene is frequently amplified in triple negative breast cancer (TNBC). Here, we show that MYC suppression induces immune-related hallmark gene set signatures and tumor infiltrating T cells in MYC-hyperactivated TNBCs. Mechanistically, MYC repressed stimulator of interferon genes (STING) expression via direct binding to the STING enhancer region, resulting in downregulation of the T cell chemokines CCL5, CXCL10 and CXCL11. In primary and metastatic TNBC cohorts, tumors with high MYC expression or activity exhibited low STING expression. Using a CRISPR-mediated enhancer perturbation approach, we demonstrated that MYC-driven immune evasion is mediated by STING repression. STING repression induced resistance to PD-L1 blockade in mouse models of TNBC. Finally, a small molecule inhibitor of MYC combined with PD-L1 blockade elicited a durable response in immune-cold TNBC with high MYC levels, suggesting a strategy to restore PD-L1 inhibitor sensitivity in MYC-overexpressing TNBC.

2022-03-01 | GSE196324 | GEO

Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [RNA-seq]

2022-03-01 | GSE196323 | GEO

An HIV protein mediates immune evasion by targeting cGAS–STING signaling

Project description:The cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of HIV-1 and initiate the antiviral immune response through cGAS–STING–TBK1–IRF3–type I IFN (IFN-I) signaling cascade. HIV-1 uses several strategies to interfere with the host immune molecules and mediate immune evasion. However, the potential role of HIV-1 proteins in cGAS–STING signaling remains unclear. Here we report that the HIV-1 protein p6 suppresses HIV-1-stimulated expression of IFN-I and promotes the immune evasion. Mechanistically, p6 bound with STING and inhibited the activation of STING and the interaction between STING and TBK1. Moreover, the glutamylation of p6 at Glu6 residue inhibited the interaction between STING and TRIM32 or AMFR, which subsequently suppressed the K27- and K63-linked polyubiquitination of STING at Lys337, therefore inhibited STING activation and type I IFN production, while the mutation of Glu6 residue lost the inhibitory effect. However, CoCl2, an agonist for cytosolic carboxypeptidases (CCPs), counteracted the glutamylation of Glu6 residue of p6 and promoted IFN-I production to block the immune evasion of HIV-1. These findings not only reveal a previously unknown mechanism through which an HIV-1 protein mediate immune evasion, but also provide a new therapeutic drug candidate to treat HIV-1 infection.

2021-11-25 | GSE189384 | GEO

Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [RNA-seq]

Project description:Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [RNA-seq]

| PRJNA804407 | ENA

Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [CHIP-seq]

Project description:Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [CHIP-seq]

| PRJNA804406 | ENA

Targeting STING–induced immune evasion with nanoparticulate binary pharmacology improves tumor control in mice

Project description:Harnessing the stimulator of interferon genes (STING) signaling pathway to trigger innate immune responses has shown remarkable promise in cancer immunotherapy; however, overwhelming resistance to intratumoral STING monotherapy has been witnessed in clinical trials, and the underlying mechanisms remain to be fully explored. Herein, we show that pharmacological STING activation following the intratumoral injection of a non-nucleotide STING agonist (i.e., MSA-2) results in apoptosis of the cytolytic T cells, interferon-mediated overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), and evasion from immune surveillance. We leverage a noncovalent chemical strategy for developing immunomodulatory binary nanoparticles (iBINP) that include both the STING agonist and an IDO1 inhibitor for treating immune-evasive tumors. This iBINP platform developed by dual prodrug engineering and subsequent nanoparticle assembly enables tumor-restricted STING activation and IDO1 inhibition, achieving immune activation while mitigating immune tolerance. A systemic treatment of preclinical models of colorectal cancer with iBINP resulted in robust antitumor immune responses, reduced infiltration of regulatory T cells, and enhanced activity of CD8+ T cells. Importantly, this platform exhibits great therapeutic efficacy by overcoming STING–induced immune evasion and controlling the progression of multiple tumor models. This study unveils the mechanisms by which STING monotherapy induces immunosuppression in the tumor microenvironment and provides a combinatorial strategy for advancing cancer immunotherapies.

2025-09-30 | GSE306421 | GEO

Epigenetic Repression of STING by MYC Promotes Immune Evasion and Resistance to Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer.

Project description:The MYC oncogene is frequently amplified in triple-negative breast cancer (TNBC). Here, we show that MYC suppression induces immune-related hallmark gene set expression and tumor-infiltrating T cells in MYC-hyperactivated TNBCs. Mechanistically, MYC repressed stimulator of interferon genes (STING) expression via direct binding to the STING1 enhancer region, resulting in downregulation of the T-cell chemokines CCL5, CXCL10, and CXCL11. In primary and metastatic TNBC cohorts, tumors with high MYC expression or activity exhibited low STING expression. Using a CRISPR-mediated enhancer perturbation approach, we demonstrated that MYC-driven immune evasion is mediated by STING repression. STING repression induced resistance to PD-L1 blockade in mouse models of TNBC. Finally, a small-molecule inhibitor of MYC combined with PD-L1 blockade elicited a durable response in immune-cold TNBC with high MYC expression, suggesting a strategy to restore PD-L1 inhibitor sensitivity in MYC-overexpressing TNBC.

| S-EPMC9250627 | biostudies-literature

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

ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lungcancer

Project description:Small cell lung cancer (SCLC) represents ~15% of all lung cancers and is characterized by its highly aggressive phenotype and its dismal outcome. Though the addition of immune checkpoint blockade to carboplatin and etoposide treatment has improved outcome in SCLC patients, SCLC cells finally acquire the ability to evade immunosurveillance and resistance against immune checkpoint blockade. To elaborate molecular mechanisms that mediate SCLC immune evasion, we performed high dimensional profiling of human and murine SCLC specimens. We herein comprehensively analyzed matched human samples of primary and metastatic SCLC and found a loss of MHC-I in SCLC metastases indicating that MHC-I loss mediates SCLC immune evasion. Silencing MHC-I in SCLC cells drastically diminished immune cell infiltration and facilitated the formation of metastasis in mice by circumventing immune surveillance. Using mass spectrometry and phospho-tyrosine kinase analysis, we discovered that ERBB2 signaling suppresses MHC-I expression in SCLC cells and stimulates immune modulating transcripts. Mechanistically, genetic and/or pharmacologic blockade of the ERBB2 signaling axis was sufficient to induce MHC-I expression and to prevent immune evasion in autochthonous murine SCLC in a STING-dependent manner. Finally, we demonstrate that the ERBB2 signaling axis regulates MHC-I expression on SCLC cells and is critical in maintaining immune evasion in SCLC. Most strikingly, we here uncover synergistic treatment efficacy by combining ERBB2 inhibition with PD-1 blockade eliciting profound responses in preclinical SCLC models, suggesting this combination for future clinical trials in patients with SCLC.

2025-10-15 | PXD065735 | Pride

An HIV protein mediates immune evasion by targeting cGAS–STING signaling

Project description:An HIV protein mediates immune evasion by targeting cGAS–STING signaling

| PRJNA782882 | ENA