Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PHF8 enables immune evasion by silencing endogenous retroelements [RNA-Seq]

ABSTRACT: Immunotherapy is currently a prime approach to cancer treatment. Despite the promise of immunotherapies such as immune checkpoint blockade on multiple cancers, most patients do not have a response or become resistant to treatment. Recent work indicate that epigenetic therapies converge with cancer immunotherapy through ‘viral mimicry’, the antiviral response triggered by endogenous nuclei acids that derived from aberrantly transcribed endogenous retrotransposons. However, epigenetic factors that regulate endogenous retrotransposons and further modulate the immune sensitivity of tumor cells is largely unknown. Here we identified the histone demethylase PHD finger protein 8 (PHF8, KDM7B), a Jumonji C domain-containing protein that erases repressive histone marks as an essential mediator of immune escape. We found that depletion of PHF8 abrogates tumor growth, induces immune memory and augments sensitivity to immune checkpoint blockade in multiple tumor models without directly affecting tumor cell proliferation.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE211474 | GEO | 2023/05/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PHF8 enables immune evasion by silencing endogenous retroelements [ATAC-seq]

Project description:Immunotherapy is currently a prime approach to cancer treatment. Despite the promise of immunotherapies such as immune checkpoint blockade on multiple cancers, most patients do not have a response or become resistant to treatment. Recent work indicate that epigenetic therapies converge with cancer immunotherapy through ‘viral mimicry’, the antiviral response triggered by endogenous nuclei acids that derived from aberrantly transcribed endogenous retrotransposons. However, epigenetic factors that regulate endogenous retrotransposons and further modulate the immune sensitivity of tumor cells is largely unknown. Here we identified the histone demethylase PHD finger protein 8 (PHF8, KDM7B), a Jumonji C domain-containing protein that erases repressive histone marks as an essential mediator of immune escape. We found that depletion of PHF8 abrogates tumor growth, induces immune memory and augments sensitivity to immune checkpoint blockade in multiple tumor models without directly affecting tumor cell proliferation.

2023-05-24 | GSE211525 | GEO

PHF8 enables immune evasion by silencing endogenous retroelements [CHIP-seq]

2023-05-24 | GSE211524 | GEO

PHF8 enables immune evasion by silencing endogenous retroelements [ChIP-seq]

2023-05-24 | GSE212778 | 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

Pharmacologic modulation of RNA splicing enhances anti-tumor immunity.

Project description:Although mutations in DNA are the best-studied source of neoantigens that determine response to immune checkpoint blockade, alterations in RNA splicing within cancer cells could similarly result in neoepitope production. However, the endogenous antigenicity and clinical potential of such splicing-derived epitopes have not been tested. Here, we demonstrate that pharmacologic modulation of splicing via specific drug classes generates bona fide neoantigens and elicits anti-tumor immunity, augmenting checkpoint immunotherapy. Splicing modulation inhibited tumor growth and enhanced checkpoint blockade in a manner dependent on host T cells and peptides presented on tumor MHC class I. Splicing modulation induced stereotyped splicing changes across tumor types, altering the MHC I-bound immunopeptidome to yield splicing-derived neoepitopes that trigger an anti-tumor T cell response in vivo. These data definitively identify splicing modulation as an untapped source of immunogenic peptides and provide a means to enhance response to checkpoint blockade that is readily translatable to the clinic.

2021-06-30 | GSE162818 | GEO

Chemohormonal Therapy Remodels Prostate Cancer Immune Microenvironment and Enhances Checkpoint Inhibitor-based immunotherapy

Project description:Checkpoint blockade immunotherapy is a promising strategy in cancer treatment, depending on a favorable preexisting tumor immune microenvironment. However, prostate cancer is usually considered as an immune “cold” tumor with the poor immunogenic response and low density of tumor-infiltrating immune cells. This research uses samples from prostate cancer patients showing that docetaxel-based chemohormonal therapy reprograms the immune microenvironment and increases tumor-infiltrating T cells. Mechanistically, docetaxel treatment activates the cGAS/STING pathway and induces the type I interferon signaling, which may boost T cell-mediated immune response. In a murine prostate cancer model, chemohormonal therapy sensitizes tumor-bearing mice to PD1-blockade therapy. These findings demonstrate that docetaxel-based chemohormonal therapy activates prostate cancer immunogenicity and acts cooperatively with anti-PD-1 checkpoint blockade, providing a combination immunotherapy strategy that would lead to better therapeutic benefit for prostate cancer.

2022-08-01 | GSE193898 | GEO

Tumor cell intrinsic type I interferon signaling dictates CD47-SIRPα blockade immunotherapy via metabolic reprograming [dataset 1]

Project description:Innate immune checkpoint has emerging as a highly potential target for cancer immunotherapy in recent years. The CD47-SIRPα axis is the best-studied innate checkpoint in cancer. However, the transcription profile of tumor cell duiring CD47-SIRPα blockade therapy remains unclear.

2024-06-04 | GSE235111 | GEO

Treating ICB-resistant glioma with anti-CD40 and mitotic spindle checkpoint controller BAL101553 (lisavanbulin)

Project description:drugs targeting mitosis might affect the tumor microenvironment and sensitize cancer cells to immunotherapy. BAL101553 monotherapy increased survival in immune checkpoint blockade–resistant SB28 glioblastoma tumors and synergized with anti-CD40 antibody

2021-10-23 | GSE186302 | GEO

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

Project description:Genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection. However, 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 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. SMARCAL1 loss hinders the ability of tumor cells to induce PD-L1 in response to genomic instability, enhances anti-tumor immune responses and sensitizes tumors to immune checkpoint blockade in a mouse melanoma model. Collectively, these studies uncover SMARCAL1 as a promising target for cancer immunotherapy.

2024-01-22 | GSE245447 | GEO

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

2024-01-22 | GSE245449 | GEO