Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Knockout of immunotherapy prognostic marker genes eliminates the effect of the anti-PD-1 treatment

ABSTRACT: We present a pan-cancer integrated analysis of transcriptome, exome and clinical records of patients. Herein, we identified candidate genes as potential biomarkers to predict clinical outcome of immunotherapy. We further explored the function of two IPM genes in vivo. Knockout of MALT1, which is critical for the T cell receptor signaling, can eliminate the anti-tumor effect of anti-PD-1 treatment completely by impairing the activation of CD8+ T cells. Notably, knockout of CLEC4D, a C-type lectin receptor that expressed on myeloid cells, also reduced the effect of anti-PD-1 treatment potentially through maintaining the immunosuppressive effects of myeloid cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE158056 | GEO | 2020/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA-seq of E0771-Vector control, E0771-Malt1-WT and E0771 Malt1-PD (Without T cell coculture)

Project description:To reveal the downstream paracrine signals from WT-Matl1 or PD-Malt1 tumor cells which responsible for the above observed macrophage phenotypes, we collected mRNA samples from Vector control-, WT-Malt1-, PD-Malt1-, V87R-Malt1-, or L88D-Malt1-expressing E0771 cancer cells, and performed RNA-seq analysis.

2024-04-18 | GSE242878 | GEO

Gene expression profile at single cell level of CD45+ immune cells from E0771-Vector control tumor tissue, E0771 wildtype Malt1 overexpression tumor tissue and E0771 paracaspase-deficient Malt1 overexpression tumor tissue.

Project description:To invesitigate the additional paracaspase-independent tumor-promoting effect exist for Malt1. We thus collected E0771-Vector control tumor tissue, E0771 wildtype Malt1 (Malt1-WT) overexpression tumor tissue and E0771 paracaspase-deficient Malt1 (Malt1-PD) overexpression tumor tissue, and sorted out immune cells for 10× Genomics single cell RNA-sequencing (scRNA-seq).

2024-04-18 | GSE242554 | GEO

Knockout of immunotherapy prognostic marker genes eliminates the effect of the anti-PD-1 treatment

Project description:Knockout of immunotherapy prognostic marker genes eliminates the effect of the anti-PD-1 treatment

| PRJNA663863 | ENA

Blockade of IL-1b and PD-1 with combination chemotherapy reduces systemic myeloid suppression in metastatic pancreatic cancer with heterogeneous effects in the tumor

Project description:Clinical and translational results from a phase Ib trial testing whether IL-1β blockade in human pancreatic cancer would alleviate myeloid immunosuppression and reveal anti-tumor T cell responses to PD-1 blockade.

2024-07-01 | GSE267814 | GEO

RNA-Seq analysis to compare myeloid cells from PD-L1-LysMCre mice with littermate Wild-type controls

Project description:Programmed death-ligand 1 (PD-L1) is predominantly expressed in the antigen-presenting cells (APCs) that are originated and abundant in bone marrow. The roles of PD-L1 in bone cell differentiation and cancer bone metastasis remain unclear. Here we show that PD-L1 antibody or PD-L1 conditional knockout in the hematopoietic or myeloid lineage suppresses osteoclast differentiation in vitro and in vivo. Bone metastases of breast cancer and melanoma are diminished by PD-L1 antibody or PD-L1 deletion in the myeloid lineage. Transcriptional profiling of bone marrow cells reveals that PD-L1 deletion in the myeloid cells up-regulates immune stimulatory genes, leading to increased macrophage M1 polarization, decreased M2 polarization, enhanced IFN? signaling, and elevated T cell recruitment and activation. All these alterations result in heightened anti-tumor immunity in the cancer microenvironment. Our findings support PD-L1 antibody as a potent therapy for bone metastasis of breast cancer and melanoma by simultaneously suppressing osteoclast and enhancing immunity.

2022-03-07 | GSE190715 | GEO

Oleuropein reprograms the immunosuppressive footprint of tumor-associated myeloid cells and enhances PD-L1/PD-1 blockade immunotherapy in cancer

Project description:Therapies based on PD-1/PD-L1 blockade fail in most cancer patients. Here we evaluated the capacities of oleuropein to reprogram tumor-associated immunosuppressive myeloid cells to increase the potency of immunotherapies. Oleuropein caused major global reprogramming of monocytic and granulocytic myeloid-derived suppressor cells and tumor-associated macrophages towards immunostimulatory subsets. Differential quantitative proteomics uncovered activated and down-modulated pathways at high resolution for each subset which regulated major differentiation programs. Oleuropein significantly potentiated the capacities of myeloid cells to activate T-cells and enhanced antitumor properties of PD-1 blockade, either by systemic anti-PD-1 antibody administration, or locally by intratumor antibody delivery with a self-amplifying RNA vector based on Semliki Forest virus. Combination therapies decreased tumor infiltration by immunosuppressive myeloid cells and increased dendritic cell recruitment within draining lymph nodes, leading to systemic antitumor T-cell responses. Potent therapeutic activities were evident in lung cancer models resistant to immunotherapies and in colon cancer models.

2024-12-08 | PXD047616 | JPOST Repository

Combined PD-L1/TGFb blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors

Project description:TGFb signaling is a major pathway associated with poor clinical outcome in patients with advanced metastatic cancers and non-response to immune checkpoint blockade, particularly in the immune-excluded tumor phenotype. While previous pre-clinical studies demonstrated that converting tumors from an excluded to an inflamed phenotype and curative anti-tumor immunity require attenuation of both PD-L1 and TGFb signaling, the underlying cellular mechanisms remain unclear. Recent studies suggest that stem cell-like CD8 T cells (TSCL) can differentiate into non-exhausted CD8 T effector cells that drive durable anti-tumor immunity. Here, we show that TGFb and PD-L1 restrain TSCL expansion as well as replacement of progenitor exhausted and dysfunctional CD8 T cells with non-exhausted IFNghi CD8 T effector cells in the tumor microenvironment (TME). Blockade of TGFb and PD-L1 generated IFNghi CD8 T effector cells with enhanced motility, enabling both their accumulation in the TME and increased interaction with other cell types. Ensuing IFNg signaling markedly transformed myeloid, stromal, and tumor niches to yield a broadly immune-supportive ecosystem. Blocking IFNg completely abolished the effect of anti-PD-L1/ TGFb combination therapy. Our data suggest that TGFb works in concert with PD-L1 to prevent TSCL expansion and replacement of exhausted CD8 T cells with fresh CD8 T effector cells, thereby maintaining the CD8 T cell compartment in a dysfunctional state.

2023-06-16 | MSV000092193 | MassIVE

PD-1 Knockout Engineered T Cells for Advanced Colorectal Cancer with MSI high expression

Project description:Interventions: experimental group :PD-1 Knockout Engineered T Cells Primary outcome(s): Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients Study Design: historical control

| 2662961 | ecrin-mdr-crc

Malt1 protease is critical in maintaining function of Treg cells and may be a therapeutic target for anti-tumor immunity

Project description:We report that the paracaspase Malt1 is required for the development and function of Treg cells. By generating Malt1 conditional knockout and protease dead mutant mice, we found Malt1-loss in Treg cells would lead to early-onset lethal autoimmune disease and the mice would die within 40 days after birth. Interestingly, mice with Treg specific inhibition of Malt1 protease activity develop spontaneous inflammatory disorders.

2018-12-20 | GSE124089 | GEO

RNA-seq of E0771-Vector control, E0771-Malt1-WT and E0771 Malt1-PD after T cell killing

Project description:To understand potential downstream signaling molecules that are responsible for wild type-Malt1 induced resistance of tumor cell to CD8 T cell killing , we first use E0771 cells expressing either -Vector control, wild type-Malt1 (M-WT), or Malt1 PD mutant (M-PD) to coculture with activated CD8 T cell at a effctor: target ratio(E:T ration) of 3 for 12 hours. Then wash the cells with PBS, digest the cells by 0.25% trypsin solution, harvest the cells in 15 ml tubes by centrifugation (1000 rpm 5min) and seed cells into the original plate with DMEM+10%FBS+1%P/S medium. 6 hours after sseding, wash cells with PBS, lyse cells with TRIZOL for RNA extraction, perform reverse transcription and cDNA library for RNA-Seq analysis.

2024-04-18 | GSE242764 | 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