Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhibition of MBTPS1 reprograms cold into inflamed tumors and potentiates anti-PD-1 immunotherapy

ABSTRACT: Despite notable advancements in cancer immunotherapy, the overall response rate among cancer patients remains low. Therefore, exploring strategies combining immunotherapy with adjuvant approaches to augment adaptive immune responses, such as by boosting the infiltration of T lymphocytes, is an attractive strategy. To pinpoint key regulators of tumor immunity, we developed a focused single guide RNA (sgRNA) library targeting membrane and secreted protein genes. Utilizing this library, we conducted an in vivo clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen in colorectal cancer mice model. We revealed that the loss of MBTPS1 in tumor cells enhanced anti-tumor immunity and synergized with anti-PD-1 therapy. Mechanistic studies uncovered that tumor cell-intrinsic MBTPS1 could compete with USP13 for binding with STAT1, thereby disrupting the USP13-dependent deubiquitination and stabilization of STAT1. MBTPS1 deficiency induced CXCR3+ CD8+ T cells infiltration in the tumor microenvironment by upregulating mRNA levels of Cxcl9, Cxcl10 and Cxcl11 transcribed by STAT1. Our study revealed that targeting MBTPS1 in cancer cells could turn cold tumors into inflamed ones, thereby enhancing the efficacy of anti-PD-1 blockade.

ORGANISM(S): Mus musculus

PROVIDER: GSE262868 | GEO | 2025/03/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Inhibition of MBTPS1 reprograms cold into inflamed tumors and potentiates anti-PD-1 immunotherapy [scRNA-seq]

Project description:Despite notable advancements in cancer immunotherapy, the overall response rate among cancer patients remains low. Therefore, exploring strategies combining immunotherapy with adjuvant approaches to augment adaptive immune responses, such as by boosting the infiltration of T lymphocytes, is an attractive strategy. To pinpoint key regulators of tumor immunity, we developed a focused single guide RNA (sgRNA) library targeting membrane and secreted protein genes. Utilizing this library, we conducted an in vivo clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen in colorectal cancer mice model. We revealed that the loss of MBTPS1 in tumor cells enhanced anti-tumor immunity and synergized with anti-PD-1 therapy. Mechanistic studies uncovered that tumor cell-intrinsic MBTPS1 could compete with USP13 for binding with STAT1, thereby disrupting the USP13-dependent deubiquitination and stabilization of STAT1. MBTPS1 deficiency induced CXCR3+ CD8+ T cells infiltration in the tumor microenvironment by upregulating mRNA levels of Cxcl9, Cxcl10 and Cxcl11 transcribed by STAT1. Our study revealed that targeting MBTPS1 in cancer cells could turn cold tumors into inflamed ones, thereby enhancing the efficacy of anti-PD-1 blockade.

2025-03-14 | GSE263524 | GEO

Inhibition of MBTPS1 reprograms cold into inflamed tumors and potentiates anti-PD-1 immunotherapy

Project description:Inhibition of MBTPS1 reprograms cold into inflamed tumors and potentiates anti-PD-1 immunotherapy

| PRJNA1094412 | ENA

Inhibition of MBTPS1 reprograms cold into inflamed tumors and potentiates anti-PD-1 immunotherapy [scRNA-seq]

Project description:Inhibition of MBTPS1 reprograms cold into inflamed tumors and potentiates anti-PD-1 immunotherapy [scRNA-seq]

| PRJNA1097966 | ENA

LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade

Project description:Chromatin regulators play a broad role in regulating gene expression, and when gone awry, can lead to cancer. Here we demonstrate that ablation of the histone demethylase LSD1 in cancer cells increases repetitive element expression, including ERVs, and decreases expression of RNA-induced silencing complex (RISC) components. Significantly, this leads to dsRNA stress and activation of type 1 interferon, which stimulates anti-tumor T cell immunity and restrains tumor growth. Furthermore, LSD1 depletion enhances tumor immunogenicity and T cell infiltration in poorly immunogenic tumors, and elicits significant responses of checkpoint blockade-refractory mouse melanoma to anti-PD-1 therapy. Consistently, TCGA data analysis shows an inverse correlation between LSD1 expression and CD8+ T cell infiltration in various human cancers. Our study identifies LSD1 as a potent inhibitor of anti-tumor immunity and responsiveness to immunotherapy, and suggests LSD1 inhibition combined with PD-(L)1 blockade as a novel cancer treatment strategy.

2018-06-21 | GSE112230 | GEO

Combinational targeting CCL7 and Flt3L to promote the expansion and infiltration of cDC1 in tumors enhances T cell activation and anti-PD-1 therapy [CD8 T]

Project description:Immune checkpoint inhibitors (ICIs) represented by anti-PD-1/PD-L1 antibodies have been widely applied for various cancers and the response rate to ICIs is closely associated with the tumor immune microenvironment (TIME). Here, we show that combinational targeting CCL7 and Fms-like tyrosine kinase 3 ligand (Flt3L) increases the infiltration and expansion of conventional type 1 dendritic cells (cDC1s) in tumor sites and enhances the T cell antitumor responses and the efficacy of anti-PD-1 therapy in subcutaneous tumor models and spontaneous KrasG12D non-small cell lung cancer (NSCLC) models. We demonstrate that the fusion protein PD-1Ab7 in which CCL7 is fused with the single chain fragment variable region of anti-PD-1 antibody (PD-1Ab) exhibits superior antitumor activities compared to PD-1Ab. Mechanistically, PD-1Ab7 promotes antitumor immunity by increasing the infiltration of cDC1s and the activation of T cells, which is severely compromised by depletion of Zbtb46+ cDCs or inhibition of the CCL7 receptor CCR2. Furthermore, complementation of Flt3L sensitizes the ICI-resistant tumors to PD-1Ab7 and synergizes with PD-1Ab7 to inhibit tumor progression. These findings highlight the essential roles of PD-1Ab-based chemokine fusion strategy in targeting cDC1s and T cells for cancer prevention and provide therapeutic lead molecules for antitumor immunotherapy.

2023-02-18 | GSE225163 | GEO

Combinational targeting CCL7 and Flt3L to promote the expansion and infiltration of cDC1 in tumors enhances T cell activation and anti-PD-1 therapy [Dendritic Cell]

2023-02-18 | GSE225126 | GEO

Comparison of osteocyte-enriched bone from DMP1 cre Mbtps1 knockout mice with littermate controls.

Project description:Purpose of arrays were to determine what the effect of deletion of Mbtps1 gene was on gene expression of osteocytes in bone in vivo. DMP1 cre driver was used to delete the Mbtps1 gene in osteocytes and osteoblasts in bone. We then isolated osteocyte enriched bone particles from 40 week old male mice to determine the effect of this deletion on gene expression. We have previously shown that Mbtps1 is needed for transcription of Phex, DMP1, and MEPE genes in osteoblasts in culture. Arrays showed these genes were reduced as expected in osteocytes in vivo. Controls represent osteocyte enriched bone from 40 week old littermates. Also, as expected, Mbtps1 expression was reduced in these knockout mice

2015-12-29 | GSE69975 | GEO

Alterations of Ceramide Synthesis Induce PD-L1 Internalization and Signaling to Regulate Tumor Metastasis and Immunotherapy Response

Project description:Programmed death-ligand 1, PD-L1 (CD274) facilitates immune evasion and exerts pro-survival functions in cancer cells. Here, we report a new mechanism whereby internalization of PD-L1 in response to alterations of bioactive lipid/ceramide metabolism by ceramide synthase 4 (CerS4) induces sonic-hedgehog (Shh) and TGF- receptor signaling to enhance tumor metastasis in triple-negative breast cancers (TNBC), exhibiting immunotherapy resistance. Mechanistically, data showed that internalized PD-L1 interacts with an RNA-binding protein Caprin-1 to stabilize Shh/TGFBR1/Wnt mRNAs to induce -catenin signaling and TNBC growth/metastasis, consistent with increased infiltration of FoxP3+ T regs and resistance to immunotherapy. While mammary tumors developed in MMTV-PyMT/CerS4-/- were highly metastatic, targeting the Shh/PD-L1 axis using Sonidegib and anti-PD-L1 antibody vastly decreased tumor growth and metastasis, consistent with the inhibition of PD-L1 internalization and Shh/Wnt signaling, restoring anti-tumor immune response. These data, validated in clinical samples and databases, provide a mechanism-based therapeutic strategy to improve immunotherapy responses in metastatic TNBCs.

2024-07-07 | GSE267312 | GEO

Effect of PLA2G10 treatment on activated human primary T cells.

Project description:T lymphocytes are frequently excluded from human cancer tissue even if T cell-recruiting chemokines are present. These observations implicate the presence of T cell excluders (TCEs) in the tumor microenvironment. We report here that phospholipase A2 group 10 (PLA2G10) protein is a potent TCE to inhibit chemokine-induced T cell mobility. Overexpression of PLA2G10 is broadly found in human cancers and is associated with poor T cell infiltration in tumor tissues. Secreted PLA2G10 in the blood is correlated with the resistance to anti-programmed cell death (PD) immunotherapy in lung cancer patients. Overexpression of PLA2G10 in immunogenic mouse tumors could exclude T cells leading to their resistance to anti-PD immunotherapy. PLA2G10 hydrolyzes phospholipids into small lipid metabolites that could mediate the inhibition of T cell mobility. Our results discover a functional antagonist of chemokines, a molecular mechanism underpinning T cell exclusion in human cancer, and implicate a potential target for cancer immunotherapy.

2022-07-21 | GSE208390 | GEO

Targeting the RNA m6A reader YTHDF2 in tumor-associated macrophages shapes tumor immunity and immunotherapy [scRNA-seq]

Project description:The presence of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) affects cancer progression and immunotherapy response. The RNA m6A methylation, an epigenetic modification, has recently been found to play a pivotal role in shaping the TME. However, the role and underlying mechanisms by which RNA m6A methylation regulates TAMs function and anti-tumor immunity remain elusive. Here we show that depletion of YTHDF2, a well-known m6A reader, in TAMs suppresses tumor growth and metastasis. Myeloid YTHDF2 deficiency reprograms TAMs to anti-tumorigenic type and increases their cross-presentation ability, thereby enhancing CD8+T cell-mediated anti-tumor immunity. Transcriptome-wide screening identifies YTHDF2 deficiency facilitates anti-tumorigenic TAMs reprogramming through targeting IFN-γ-STAT1 signaling. Selectively targeting YTHDF2 in TAMs using toll-like receptor 9 agonist - conjugated small interfering RNA against YTHDF2 effectively promotes anti-tumor immunity, restrains tumor growth, and enhances the efficacy of anti-PD-L1 therapy. Together, our findings suggest that YTHDF2 in TAMs might be a promising therapeutic target for cancer immunotherapy.

2022-08-01 | GSE189193 | 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